Mattias Aurell |
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Bendz H, Aurell M, Lanke J. A historical cohort study of kidney damage in long-term lithium patients: continued surveillance needed. Eur Psychiatry 2001; 16(4):199-206. BACKGROUND: Insufficient knowledge on the longitudinal fate of renal function in lithium patients incited this retrospective study of 149 patients. METHOD: Medical record review of a lithium cohort (N = 149), 8--12 years after an initial renal function study. RESULTS: Twenty-one patients had died, one from uremia probably not caused by lithium, and 42 had discontinued lithium. Reduced urinary concentrating capacity (Umax) or glomerular filtration rate (GFR) was not more frequent among deceased or off-lithium patients than among the 86 patients who were on lithium at follow-up. In 63 of the latter patients, Umax had been re-examined after the initial study, and GFR in 29 patients. Reduced Umax and GFR had become twice as common, and average Umax and GFR had decreased significantly. The reduction of GFR was associated with lithium treatment duration and age, and reduced Umax with treatment duration only. CONCLUSIONS: Reduced renal function is not a major cause of treatment discontinuation but becomes increasingly common with treatment duration.Limitations. Missing data rendered the interpretation difficult in some respects.Clinical relevance. The increased proportion of patients with reduced GFR and Umax with time implies an increased risk of potentially lethal dehydration and lithium intoxication. Continued surveillance of urinary output and GFR is therefore necessary. 7439-93-2 (Lithium); Aurell M. Varfor motarbetas frivillig specialistexamen? Lakartidningen 2000; 97(5):505. English title: "Why against the voluntary specialists' examination?" Clinical Competence; Education, Medical, Continuing; Educational Measurement; Human; Sweden; Johansson M, Jensen G, Aurell M, Friberg P, Herlitz H, Klingenstierna H et al. Evaluation of duplex ultrasound and captopril renography for detection of renovascular hypertension. Kidney Int 2000; 58(2):774-82. BACKGROUND: Renovascular hypertension is the most common form of curable secondary hypertension and, if untreated, may lead to end-stage kidney disease. Given that renal function and hypertension may improve after renal angioplasty, it is pertinent to identify patients with renal artery stenosis. The aim of the present study was to evaluate both duplex ultrasound and captopril renography for detection of renal artery stenosis among hypertensive patients. METHODS: To avoid selection bias, all patients referred to our center for evaluation of renovascular hypertension were asked to participate in the study. Patients were examined by intra-renal duplex ultrasound (N = 121), measuring pulsatility index and acceleration of the blood flow during early systole. In 98 patients, 99mTc-DTPA captopril renography was performed in conjunction with duplex ultrasound. Renal angiography was performed in all patients regardless of the results of the noninvasive tests. RESULTS: The prevalence of renal artery stenosis was 19%. In the 98 patients examined by both duplex ultrasound and captopril renography, sensitivity and positive predictive values for detection of a renal artery stenosis of 50% degree or more were 84 and 76%, respectively, for duplex ultrasound, whereas captopril renography was associated with a sensitivity and positive predictive value of 68% for both (P = NS). Specificity and negative predictive values were 94 and 96%, respectively, for duplex ultrasound, whereas the corresponding values for captopril renography were 92% for both (P = NS). Specificity and negative predictive values were 94 and 96%, respectively, for duplex ultrasound, whereas the corresponding values for captopril renography were 92% for both (P = NS). CONCLUSIONS: Both duplex ultrasound and captopril renography are associated with high specificity and negative predictive values for detection of renal artery stenosis. Sensitivity and positive predictive values are at least as good for duplex ultrasound compared with captopril renography. Given that duplex ultrasound is easier to perform and more cost effective, we propose that it should be the method of first choice when screening for renal artery stenosis in a hypertensive population. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Radiopharmaceuticals); 62571-86-2 (Captopril); 65454-61-7 (Technetium Tc 99m Pentetate); Stefansson B, Ricksten A, Rymo L, Aurell M, Herlitz H. Angiotensin-converting enzyme gene I/D polymorphism in malignant hypertension. Blood Press 2000; 9(2-3):104-9. BACKGROUND: The mechanism of the rapid transition of a stable benign hypertensive disease to a severe and devastating malignant hypertension is not fully understood. However, the renin angiotensin system, which is highly activated in malignant hypertension, is established as an important pathogenetic factor in different cardiovascular and renal diseases. Over the last decade, a polymorphism in genes regulating this system has been found. This includes the 287 bp sequence deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme (ACE) gene and the methionine (M) to threonine (T) point mutation polymorphism in the angiotensinogen (AGT) gene. These gene polymorphisms have been associated with various cardiovascular and renal diseases and the aim of this study was to investigate whether they were linked to malignant hypertension. METHODS: Forty-two patients with malignant hypertension (mean age 55 years), 42 patients with non-malignant hypertension (mean age 57 years) and 85 normotensive control subjects (mean age 42 years) were investigated with respect to ACE I/D and AGT M/T genotypes. DNA was prepared by standard methods from isolated white blood cells and analysed by the PCR technique. The PCR reaction used in the detection of the ACE I/D polymorphism was optimized for an equal amplification of the I and D alleles. RESULTS: The frequency of the DD genotype was significantly increased in patients with malignant hypertension (43%) compared with patients with non-malignant hypertension (14%) and normotensive control subjects (18%) (p <0.01) for both. The frequency distribution of AGT M/T genotype did not differ between patients with malignant and non-malignant hypertension. CONCLUSION: The DD genotype of the ACE gene occurred more than twice as often in malignant hypertension than in non-malignant hypertension and indicates that ACE gene polymorphism is a significant risk factor for initiation of malignant hypertension. 0 (DNA Transposable Elements); EC 3.4.15.1 (Peptidyl-Dipeptidase A); Aurell M. Screening for secondary hypertension. Curr Hypertens Rep 1999; 1(6):461. Human; Hypertension, Renovascular/diagnosis; Kidney Failure/prevention & control; Radioisotope Renography; Ultrasonography, Doppler, Duplex; Bendz H, Aurell M. Drug-induced diabetes insipidus: incidence, prevention and management. Drug Saf 1999; 21(6):449-56. Drug-induced diabetes insipidus is always of the nephrogenic type, i.e. unresponsiveness of the kidneys to the action of antidiuretic hormone. This condition is easily diagnosed by measuring urinary concentrating capacity during a thirst test (e.g. 12 hours of water deprivation) or by administration of a modified antidiuretic hormone, desmopressin, to demonstrate the renal unresponsiveness. Drug-induced nephrogenic diabetes insipidus is not a common disorder except in patients receiving treatment with lithium salts for affective disorders where it may affect about 10% of patients treated long term (15 years). Drug-induced nephrogenic diabetes insipidus caused by other drugs usually occurs in critically ill patients in intensive care units receiving a multitude of drugs dominated by antimicrobials and cytostatics. A search of the World Health Organization's adverse effect database revealed 359 reports of drug-induced diabetes insipidus. Lithium was the most common cause (159 reports) followed by foscarnet (15) and clozapine (10). Treatment is symptomatic in most patients and the offending drug should be stopped. If urine volumes exceed 4 L/day, treatment with thiazides and amiloride has been advocated, and nonsteroidal anti-inflammatory drugs, such as indomethacin, may be tried in severe cases. Prevention of lithium-induced nephrogenic diabetes insipidus is an important aspect of the treatment of affective disorders. In patients treated long term it appears to be only partly reversible upon lithium discontinuation. Close monitoring of the treatment aiming at 12-hour trough value of 0.4 to 0.6 mmol/L is recommended. Yearly measurement of the urinary volume/day is effective in making both the patient and the physician aware of the development of the drug-induced nephrogenic diabetes insipidus. The condition is a serious adverse effect because of the risk of developing dehydration and aggravation of drug intoxications. 7439-93-2 (Lithium); Bergstrom G, Herlitz H, Himmelmann A, Ljungman S, Aurell M. 100 ars perspektiv pa njurfunktion och hypertoni. Anti-reninterapi har gjort hypertensiv njursvikt till en raritet. Lakartidningen 1999; 96(47):5209-14. English title: "A 100-year perspective on renal function and hypertension. Anti-renin therapy has made hypertensive renal failure a rarity" One hundred years ago, in 1898, Professor Robert Tigerstedt, Karolinska institutet, Sweden, discovered renin. The subsequent elaboration in 1960 of the renin-angiotensin-aldosterone system signalled the start of modern hypertension research. The kidney takes part in blood pressure regulation in a number of ways. Indications are that increased renovascular resistance due to increased renin-angiotensin activity is of importance for the barostatic function of the kidneys and for the pathogenesis of human hypertension. Several commonly used, efficacious and well tolerated antihypertensive agents act by blocking the renin-angiotensin system, thus normalising kidney function. A number of current large-scale trials--utilising ACE inhibitors and angiotensin receptor antagonists--will, it is hoped, elucidate the proper role of 'anti-renin therapy' in the treatment of hypertension. Thanks to effective modern management of hypertension, renal failure due to hypertensive kidney disease is rare in Sweden today. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antihypertensive Agents); 11128-99-7 (Angiotensin II); EC 3.4.23.15 (Renin); Aurell M. The renin-angiotensin system: the centenary jubilee. Blood Press 1998; 7(2):71-5. Animal; History of Medicine, 19th Cent.; History of Medicine, 20th Cent.; Human; Renin-Angiotensin System; Aurell M. "Gyllene decennium" for njurmedicinen. Genterapi vantas ge nya genombrott. Lakartidningen 1998; 95(23):2660-4. English title: "A golden decade" for kidney medicine. Gene therapy is expected to result in a new break through" Gene Therapy/trends; Human; Kidney/anatomy & histology; Kidney Diseases/epidemiology/genetics/therapy; Kidney Transplantation/statistics & numerical data; Models, Anatomic; Peritoneal Dialysis/statistics & numerical data; Prognosis; Renal Dialysis/statistics & numerical data; Sweden/epidemiology; Brandstrom E, Grzegorczyk A, Jacobsson L, Friberg P, Lindahl A, Aurell M. GFR measurement with iohexol and 51Cr-EDTA. A comparison of the two favoured GFR markers in Europe. Nephrol Dial Transplant 1998; 13(5):1176-82. BACKGROUND: The aim of the present study was to compare the most commonly used GFR markers for clearance measurements, 51Cr-EDTA and iohexol, using two different methods for iohexol analysis, HPLC and X-ray fluorescence, referring both to the multiple-sample and single-sample calculations, using 51Cr-EDTA as the reference method. METHODS: Forty-nine patients with an estimated GFR >40 ml/min were included. 51Cr-EDTA and iohexol were injected simultaneously and blood samples were taken 150, 195 and 240 min after injection of the respective marker. RESULTS: The multiple-point clearances, determined from HPLC and X-ray fluorescence, compared to 51Cr-EDTA correlated highly (r=0.92 and 0.95 respectively). The results from single-point clearance comparison, iohexol measured by HPLC vs 51Cr-EDTA, yielded a correlation of r=0.91, while single-point clearance from iohexol, analysed by X-ray fluorescence, obtained a correlation of 0.93 and an intercept statistically different from origo. CONCLUSIONS: Iohexol and 51Cr-EDTA are comparable as GFR markers for multiple-point clearance measurements. The single-sample method for GFR >40 ml/min can be used with a high accuracy. The precision and accuracy of X-ray fluorescence analysis of low concentrations of iohexol were less than those of HPLC. Care should therefore be taken when using X-ray fluorescence that the injected dose of iohexol should result in a plasma concentration level of iodine of at least 0.06 mg/ml at the time of blood sampling. 0 (Biological Markers); 0 (Chromium Radioisotopes); 60-00-4 (Edetic Acid); 66108-95-0 (Iohexol); Jensen G, Aurell M. Individual kidney function before and after renal angioplasty. Lancet 1998; 352(9134):1150-1. Adult; Aged; Angioplasty; Arteriosclerosis/physiopathology/therapy; Comparative Study; Glomerular Filtration Rate; Human; Kidney/physiopathology; Middle Age; Renal Artery Obstruction/therapy; Renal Circulation; Jensen G, Zachrisson BF, Volkmann R, Aurell M. Njurartarstenos--underskattad orsak till hypertoni och njursvikt? Lakartidningen 1998; 95(38):4068 4071-4. English title: "Renal artery stenosis--an underestimated cause of hypertension and renal failure?" Although renovascular hypertension is associated with substantial cardiovascular morbidity, ultimately it is a curable disease. Early identification and appropriate treatment of renovascular hypertension may save years of antihypertensive therapy, reduce the morbidity associated with long-standing hypertension, and help to minimise the risk of renal failure. However, the main problem is to identify patients with renovascular disease suitable for treatment. This requires alertness in the clinician, and renographic screening of renal function or duplex-ultrasound scanning of renovascular circulation to augment the yield of angiographic procedures. The predominant treatment of renovascular disease today is percutaneous transluminal angioplasty, which can be used as a repeat procedure or in combination with endoluminal stenting of the stenotic renal artery. Angioplasty, Balloon; Cardiovascular Diseases/etiology/prevention & control; Human; Hypertension, Renovascular/etiology/radiography/therapy/ ultrasonography; Kidney Failure/etiology/prevention & control; Renal Artery; Obstruction/complications/radiography/therapy/ultrasonography; Risk Factors; Taylor Jr AT, Fletcher JW, Nally Jr JV, Blaufox MD, Dubovsky EV, Fine EJ et al. Procedure guideline for diagnosis of renovascular hypertension. Society of Nuclear Medicine. J Nucl Med 1998; 39(7):1297-302. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Radiopharmaceuticals); Aurell M, Bengtsson C, Bjorck S. Enalapril versus metoprolol in primary hypertension--effects on the glomerular filtration rate. Nephrol Dial Transplant 1997; 12(11):2289-94. BACKGROUND: Hypertension is a significant cause of end-stage renal failure and effective treatment of hypertensive will reduce the progression rate of chronic renal failure in various kidney disorders. Different classes of drugs may be more effective than others in this respect. In this study we compared the effects on the glomerular filtration rate (GFR) of the ACE-inhibitor enalapril and the betablocker metoprolol in patients with mild and moderate primary hypertension during 6 years. METHODS: Patients with GFR in the normal range (> or = 80 ml/min/1.73 m2 BSA) were included after a placebo treatment period of 4-8 weeks if diastolic blood pressure was 100-120 mm Hg. Target blood pressure was set to < 90 mm Hg diastolic. One hundred and thirty patients were randomized in an open parallel study to receive either enalapril or metoprolol. No placebo group was included. GFR was measured using the 51CR-EDTA clearance method and 81 patients completed the study. RESULTS: At inclusion, there were no significant differences regarding GFR or blood pressure between the groups. The blood pressure treatment goal was reached in all patients and was maintained during the whole observation period. A small but significant fall in GFR by 4 ml/min/1.73 m2 BSA was noted in both groups after the first year of treatment but thereafter GFR decreased by only 1 ml/min/year/1.73 m2 BSA, in both groups. Body weight, serum uric acid and triglycerides increased slightly with metoprolol treatment but no other differences between the two treatments were noted. CONCLUSIONS: With the blood pressure maintained at the same level using either enalapril or metoprolol during a 6-year study period, GFR decreased to the same extent in the two groups both during the first year and thereafter. The overall magnitude of the GFR decline approached that of the normal age-related decrease of kidney function, i.e. GFR decreased only about 1 ml/min/year. Thus, treatment with an ACE-inhibitor, enalapril, and a beta-blocker, metoprolol, protected the kidney function to the same extent in this 6 year long study in mild and moderate primary hypertension. 0 (Adrenergic beta-Antagonists); 0 (Angiotensin-Converting Enzyme Inhibitors); 37350-58-6 (Metoprolol); 75847-73-3 (Enalapril); Aurell M, Jensen G. Treatment of renovascular hypertension. Nephron 1997; 75(4):373-83. Animal; Human; Hypertension, Renovascular/diagnosis/etiology/physiopathology/ therapy; Johnsen SA, Persson IB, Aurell M. PGE2 production after angiotensin-converting enzyme inhibition. Scand J Urol Nephrol 1997; 31(1):81-8. Using OKT3 monoclonal antibody driven T-lymphocyte proliferation, we investigated the effects of plasma 10, 20 and 30% in cell cultures on the proliferation ex vivo after exposure to captopril or enalapril taken orally by healthy volunteers. We also studied the effects of captopril, angiotensin II and bradykinin in vitro. We observed a plasma dependent dual effect of ACE inhibition both ex vivo and in vitro and of bradykinin in vitro being a stimulated proliferation at low (10% plasma) and a suppression of proliferation at high (30% plasma). The suppression was shown to be PGE2 mediated but the nature of the stimulatory signal is unknown. Proliferation was also suppressed by angiotensin II mediated by PGE2, but angiotensin II had no stimulatory effect. The results indicate that the effects of ACE inhibition on OKT3 mAb driven T-lymphocyte proliferation is plasma dependent, class specific for ACE inhibitors and mediated by both the ACE inhibitor itself and by bradykinin. Furthermore, it was shown that indomethacin in combination with an ACE inhibitor or bradykinin converted a suppressive response into proliferation indicating an immunostimulatory activity by indomethacin. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Muromonab-CD3); 11128-99-7 (Angiotensin II); 363-24-6 (Dinoprostone); 53-86-1 (Indomethacin); 58-82-2 (Bradykinin); 62571-86-2 (Captopril); 75847-73-3 (Enalapril); Bendz H, Sjodin I, Aurell M. Renal function on and off lithium in patients treated with lithium for 15 years or more. A controlled, prospective lithium-withdrawal study. Nephrol Dial Transplant 1996; 11(3):457-60. BACKGROUND. Controversy remains over the magnitude and reversibility of reduced renal function in long-term lithium patients. METHODS. Thirteen patients with 18 years (range 15-24) on lithium discontinued the treatment, and were re-examined twice after 5 and 9 weeks (4-16) off lithium. They were compared to a non-lithium psychiatric control group, matched for age and sex. RESULTS. Glomerular filtration rate (GFR) tended to improve from 69 (39-96) to 74 (39-94) ml/min/1.73 m2 BSA, P = 0.057, which was not significantly different from 78 (61-106 ml/min per 1.73 m2 BSA in the controls. Reduced GFR was found in only two of the lithium patients off lithium, and in none of the controls. Maximal urinary concentrating capacity did not improve at all. It was 637 (130-875) mOsm/kg H2O in the lithium patients, which was lower than 856 (705-1.035) mOsm/kg H2O (P < 0.01) in the controls. Two of the lithium patients had isosthenuria. CONCLUSIONS. Lithium patients often have an irreversible, clinically important reduction of Umax, sometimes progressing to nephrogenic diabetes insipidus, while GFR is well preserved in most patients. 60-27-5 (Creatinine); 7439-93-2 (Lithium); Blaufox MD, Aurell M, Bubeck B, Fommei E, Piepsz A, Russell C et al. Report of the Radionuclides in Nephrourology Committee on renal clearance. J Nucl Med 1996; 37(11):1883-90. The need for simple and accurate methods to measure renal function is self-evident. This need increases as techniques for intervention become available. The demand for evaluation of individual kidney function has increased with its role in the diagnosis and follow-up of unilateral renal disease and in decision making for conservative or surgical treatment based on residual renal function. The role of nuclear medicine in this area has been inhibited by confusion about conflicting methodologies. This report is meant to provide guidance to those centers that would like to initiate clearance procedures but have difficulty in choosing appropriate methodology. 0 (Radiopharmaceuticals); Himmelmann A, Bergbrant A, Svensson A, Hansson L, Aurell M. Remikiren (Ro 42-5892)--an orally active renin inhibitor in essential hypertension. Effects on blood pressure and the renin-angiotensin-aldosterone system. Am J Hypertens 1996; 9(6):517-22. Remikiren (Ro 42-5892) is a new orally active renin inhibitor with high potency and specificity in vitro. In the present study, the drug was given in a short-term study in patients with essential hypertension, either as monotherapy or with added hydrochlorothiazide. Following a wash-out period of at least 3 weeks and then 8 days of single-blind placebo, 29 patients with essential hypertension were given remikiren 600 mg orally for 8 days. After 4 days of remikiren, hydrochlorothiazide 12.5 mg or 25 mg or placebo was added in double-blind fashion for the last 4 days. There were no significant changes in blood pressure in patients given remikiren alone. In patients given additional hydrochlorothiazide for 4 days, a marked reduction in blood pressure was observed. Remikiren effectively inhibited the plasma renin activity 24 h post-dose, whereas angiotensin II was reduced only during the first hours after drug administration. It is concluded that remikiren is orally effective. Its antihypertensive effect during short-term administration was not significant, but when given with a diuretic, a marked potentiation occurred. Further studies are needed to establish the long-term effects of remikiren alone and in combination therapy. 0 (Antihypertensive Agents); 0 (Diuretics, Thiazide); 0 (Enzyme Inhibitors); 0 (Imidazoles); 135669-48-6 (Ro 42-5892); 58-93-5 (Hydrochlorothiazide); EC 3.4.23.15 (Renin); O'Reilly P, Aurell M, Britton K, Kletter K, Rosenthal L, Testa T. Consensus on diuresis renography for investigating the dilated upper urinary tract. Radionuclides in Nephrourology Group. Consensus Committee on Diuresis Renography. J Nucl Med 1996; 37(11):1872-6. There is great variation in technique and interpretation of diuresis renography between different establishments. METHODS: To address this problem, an International Consensus Committee was appointed by the Ninth International Symposium on Radionuclides in Nephrourology in 1994. RESULTS: The final document was produced and addressed: objectives, equipment, data acquisition, choice of radiopharmaceutical, patient preparation, position, dosage of furosemide, timing of furosemide, role of bladder catheter, duration of study, pediatric considerations, evaluation of the furosemide response, interpretation, and conclusion. CONCLUSION: The report presents a standardized approach to diuresis renography that, if adopted, will improve reproducibility between centers, discourage unacceptable practice and stimulate further discussion between nuclear medicine and urology health care professionals who treat patients with dilated and obstructed upper urinary tracts. 0 (Diuretics, Sulfamyl); 54-31-9 (Furosemide); Taylor A, Nally J, Aurell M, Blaufox D, Dondi M, Dubovsky E et al. Consensus report on ACE inhibitor renography for detecting renovascular hypertension. Radionuclides in Nephrourology Group. Consensus Group on ACEI Renography. J Nucl Med 1996; 37(11):1876-82. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Iodine Radioisotopes); 125224-05-7 (Technetium Tc 99m Mertiatide); 147-58-0 (Iodohippuric Acid); 65454-61-7 (Technetium Tc 99m Pentetate); Aurell M, Samuelsson B, Breimer M, Bjorck S, Rydberg L. Forsta delmal natt i xenotransplantationsprojekt: grisnjure i human cirkulation. Lakartidningen 1995; 92(26-27):2655-6. English title: "The first part of the goal of a project on xenotransplantation is achieved: porcine kidney in human circulation" Animal; Human; Kidney Transplantation; Research; Sweden; Swine; Transplantation, Heterologous; Jensen G, Zachrisson BF, Delin K, Volkmann R, Aurell M. Treatment of renovascular hypertension: one year results of renal angioplasty. Kidney Int 1995; 48(6):1936-45. During the ten year period from 1981 to 1991, percutaneous transluminal renal angioplasty (PTRA) was performed in 180 renal arteries in 137 patients, where the underlying renovascular disease was fibromuscular dysplasia (FMD) in 30 patients (22%) and arteriosclerotic vascular disease (AVD) in 107 (78%). A preinterventional work-up and a re-evaluation of the patients after one year was designed for the assessment of the clinical, functional and technical outcome. Successful technical dilatation was achieved in 97% of procedures with FMD patients and in 82% of procedures with AVD patients. A beneficial effect on the blood pressure and the renal function was registered in both groups. The overall cure and improvement rate for hypertension was 86% in the FMD group and 64% in the AVD group after one year's follow-up. A significant gain in the total renal function was registered in both groups, the average increase in glomerular filtration rate being 13% (P < 0.001) for the FMD group and 11% (P < 0.001) for the AVD group one year after PTRA. Renal function was improved or unchanged in 89% of FMD patients and 74% of AVD patients. The improvement in renal function was made by the revascularized kidney. Renal vein renin investigation predicted the clinical outcome with an excellent diagnostic accuracy as no renin negative patient became normotensive, and renin positive patients, who did not turn normotensive, were in almost 90% of the cases affected by technical failure or restenosis/contralateral stenosis. Thus, the sensitivity of renal vein renin investigation was 95% and the specificity 75%. The outcome for patients with hypertension and renal insufficiency was considerably poorer than for the whole group of patients, with only a 20% success rate for hypertension, but 50% in this group had increased or unchanged GFR after intervention. The angiographic one-year follow-up revealed a recurrence rate of 6.7% for FMD and 15.1% for AVD. For the entire series of patients, the incidence of major complications was 5.4%, including one indirect fatality, while the incidence of minor complications was 5%. In conclusion, PTRA will cure or improve blood pressure in most patients with renovascular hypertension, and it preserves and even improves renal function in these patients. Complications and recurrence are in fact not very common and PTRA appears be the best first approach in all but ostial lesions for treatment of renovascular hypertension. Angioplasty, Balloon/methods; Human; Hypertension, Renovascular/physiopathology/radiography/therapy; Kidney Function Tests; Renal Artery/radiography; Retrospective Studies; Treatment Outcome; Aurell M. Accurate and feasible measurements of GFR--is the iohexol clearance the answer? Nephrol Dial Transplant 1994; 9(9):1222-4. 66108-95-0 (Iohexol); 9005-80-5 (Inulin); Bendz H, Aurell M, Balldin J, Mathe AA, Sjodin I. Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium. Nephrol Dial Transplant 1994; 9(9):1250-4. The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected. 7439-93-2 (Lithium); Herlitz H, Widgren B, Wikstrand J, Aurell M. Abnormalities in the renin-angiotensin-aldosterone system in normotensive subjects with a positive family history of hypertension. Eur J Endocrinol 1994; 131(2):179-83. Non-hypertensive men with a positive family history of hypertension in two generations (N = 16) were compared with weight-matched (N = 13) and lean (N = 12) control groups with a negative family history of hypertension with respect to the activity of the renin-angiotensin-aldosterone system at baseline and during an oral glucose tolerance test. Blood pressure was measured phonographically after 30 min of semirecumbent rest and the oral glucose tolerance test was performed after a 10-h overnight fast with 100 g of glucose given orally. Blood samples were drawn from a peripheral catheter at baseline, 30 and 120 min after the glucose challenge. Systolic and diastolic blood pressures did not differ between subjects with a positive or a negative family history of hypertension. At baseline, blood glucose and plasma insulin were similar in the three groups while the group with a positive family history of hypertension had a significantly lower plasma renin activity (PRA) (0.85 +/- 0.09 compared with the weight-matched but not with the lean control group (1.36 +/- 0.13 and 1.06 +/- 0.15 ng AI.ml-1.h-1; p < 0.01 and NS, respectively). The PRA increased significantly after the glucose challenge in all groups (p < 0.01), while the plasma aldosterone concentration decreased after 30 min and then showed an increase at 120 min. The PRA response was less pronounced in the group with a positive family history of hypertension compared with the weight-matched and lean control groups (p < 0.05 and p < 0.01, respectively). Serum potassium did not change significantly in either group after the glucose challenge. Urinary sodium excretion was similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) 52-39-1 (Aldosterone); EC 3.4.23.15 (Renin); Jensen G, Bardelli M, Volkmann R, Caidahl K, Rose G, Aurell M. Renovascular resistance in primary hypertension: experimental variations detected by means of Doppler ultrasound. J Hypertens 1994; 12(8):959-64. OBJECTIVE: To gauge the influence of renovascular resistance changes on blood flow velocity pulsatility in kidneys of hypertensive patients by means of the ultrasonic colour and pulsed-wave Doppler method, since we have previously shown in normotensive subjects that the blood flow velocity pulsatility in renal interlobar arteries varies with changes in renovascular resistance. METHODS: In six male patients with primary hypertension, renal blood flow velocity profiles were investigated by means of duplex ultrasound. Single-kidney renovascular resistance was assessed by measurements of split renal function (gamma-camera renography), renal plasma flow (steady-state para-aminohippurate clearance) and cuff blood pressure. The pulsatility index of the blood flow velocity spectrum in the renal interlobar artery and renovascular resistance were measured either at rest, during infusion of angiotensin II, or after angiotensin converting enzyme inhibition. RESULTS: A significant correlation existed between pulsatility index and renovascular resistance (r = 0.50, P < 0.002), which did not improve after correction for the blood pressure pulsatility. Changes of pulsatility index were more closely related (r = 0.64, P < 0.001) to the corresponding changes in renovascular resistance. CONCLUSIONS: With the two-dimensional image-guided colour and pulsed-wave Doppler method it is possible to assess semiquantitatively small intra-individual changes in renovascular resistance in hypertensive patients by means of pulsatility index measurements. Pharmacologically induced alterations in renovascular haemodynamics may therefore be evaluated with this technique. 0 (Angiotensin-Converting Enzyme Inhibitors); 11128-99-7 (Angiotensin II); 61-78-9 (p-Aminohippuric Acid); Aurell M. ACE inhibition: antihypertensive treatment of choice in progressive chronic renal failure? Nephrol Dial Transplant 1993; 8(8):680-1. 0 (Angiotensin-Converting Enzyme Inhibitors); Herlitz H, Hjemdahl P, Volkmann R, Jensen G, Aurell M. Renal and systemic sympathetic counterregulation in response to vasodilators in renovascular hypertension. Clin Sci (Colch) 1993; 84(1):41-5. Twenty-two patients with renovascular hypertension and significant lateralization of renin secretion were investigated with respect to arterial and renal venous plasma noradrenaline and dopamine concentrations before and 30 min after two different blood pressure-lowering procedures (enalaprilat or dihydralazine intravenously). 2. In one group of patients (n = 10) blood pressure reduction by 7.5 mg of dihydralazine caused stimulation of the renin-angiotensin system and increased heart rate (P < 0.01) as well as arterial and renal venous plasma noradrenaline and dopamine concentrations (P < 0.01 for both). The elevation of the plasma dopamine concentration was more pronounced than that of noradrenaline, yielding increased dopamine/noradrenaline ratios both peripherally (P < 0.05) and in the renal veins (P < 0.05). 3. In the second group of patients (n = 12) a comparable reduction in blood pressure elicited by 1.25 mg of enalaprilat was not accompanied by alterations in heart rate or in noradrenaline or dopamine levels in arterial plasma or renal venous plasma from either kidney. 4. Thus, inhibition of angiotensin-converting enzyme does not elicit the expected sympathetic counter-regulatory response to blood pressure reduction; the mechanism(s) involved remains to be clarified. 0 (Vasodilator Agents); 484-23-1 (Dihydralazine); 51-41-2 (Norepinephrine); 51-61-6 (Dopamine); 84680-54-6 (Enalaprilat); Jensen G, Moonen M, Aurell M, Granerus G, Volkmann R. Reliability of ACE inhibitor-enhanced 99Tcm-DTPA gamma camera renography in the detection of renovascular hypertension. Nucl Med Commun 1993; 14(3):169-75. Twenty consecutive patients with renovascular hypertension, proven by cure or improvement of hypertension at 1-year follow-up after percutaneous transluminal angioplasty or surgical repair, were studied before intervention by means of gamma camera renography with 99Tcm-diethylenetriaminepentaacetic acid (99Tcm-DTPA) at baseline and after angiotensin-converting enzyme (ACE) inhibition. Sixteen patients underwent bilateral renal vein catheterization for measurement of renal vein renin release and extraction ratios of para-amino-hippurate (PAH) and 51Cr-EDTA before and after acute ACE inhibition. With the limit for a significant change in relative side distribution of 5% or more after ACE inhibition on gamma camera renography 13 patients responded (Group 1), while seven patients (Group 2) had unchanged side distribution. Glomerular filtration rate (GFR), measured with 99Tcm-DTPA, in the affected kidney decreased in Group 1 from 26 +/- 16 ml min-1 to 11 +/- 12 ml min1 (P < 0.0005), while GFR was unchanged in the affected kidney in Group 2, 26 +/- 13 ml min-1 versus 29 +/- 13 ml min-1. Extraction ratios of PAH and 51Cr-EDTA for the affected kidney in Group 1 decreased from 80 +/- 18 to 73 +/- 21% (P < 0.05) and from 16 +/- 5 to 7 +/- 5% (P < 0.005), respectively, while in Group 2 the PAH extraction ratio was not significantly changed, 86 +/- 5 versus 81 +/- 14%, but the 51Cr-EDTA extraction ratio for the affected kidney also decreased from 16 +/- 3 to 8 +/- 4% (P < 0.005). All patients had lateralization of renal vein renin to the affected kidney.(ABSTRACT TRUNCATED AT 250 WORDS) 62571-86-2 (Captopril); 65454-61-7 (Technetium Tc 99m Pentetate); 75847-73-3 (Enalapril); Ljungman S, Wikstrand J, Hartford M, Aurell M, Lindstedt G, Berglund G. Effects of long-term antihypertensive treatment and aging on renal function and albumin excretion in primary hypertension. Am J Hypertens 1993; 6(7 PT 1):554-63. The effects on renal function and urinary albumin excretion of 7 years of antihypertensive treatment compared to the effects of normal aging were studied in a random sample of 40 men with newly diagnosed primary hypertension and in 17 normotensive men of the same age, respectively. The hypertensives were treated with metoprolol either as monotherapy (n = 21) or combined with hydrochlorothiazide or hydralazine. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; para-aminohippurate clearance), renal vascular resistance (RVR), and the 24 h urinary albumin excretion were determined. GFR was significantly reduced from 104 +/- 15 mL/min (mean +/- SD) to 86 +/- 20 mL/min (P < .001) in the hypertensive group, but the reduction was not significantly greater than in the normotensive group. As judged from the study of a subgroup of the hypertensives, most of the decrease in GFR occurred early as an immediate drug-induced, functionally explained decrease. The changes in RBF and RVR after 7 years of treatment did not differ significantly from those due to normal aging. RVR remained higher and RBF remained lower in the hypertensives than in the normotensives. The urinary albumin excretion in the hypertensives was significantly reduced after 7 years but remained higher than in the normotensives. In conclusion, the changes in renal function and hemodynamics seen after long-term treatment with metoprolol in primary hypertension were not significantly different from the changes caused by normal aging in normotensives. 37350-58-6 (Metoprolol); 58-93-5 (Hydrochlorothiazide); 86-54-4 (Hydralazine); Metry GS, Attman PO, Lonnroth P, Beshara SN, Aurell M. Urea kinetics during hemodialysis measured by microdialysis--a novel technique. Kidney Int 1993; 44(3):622-9. A microdialysis technique has been developed for estimation of concentrations of low molecular size compounds in the interstitial fluid in vivo. With this technique urea kinetics in the interstitial fluid and plasma were studied in ten patients during and after hemodialysis. There was a close correspondence between urea measurements in plasma and interstitium during hemodialysis. Urea rebound occurred in plasma during two hours after dialysis (15.8 +/- 6.5% in the first hour and 11.8 +/- 5.9% in the second hour). The urea rebound in the interstitium was delayed about 60 minutes after that of plasma (2.8 +/- 8% and 14.1 +/- 7.8% in the first and second hours, respectively) and continued for up to four hours after dialysis. The relationship between plasma urea rebound and the efficiency of hemodialysis and ultrafiltration volume was studied in 17 patients. Results showed a close relation between the fractional urea removal during dialysis and the plasma urea rebound. The contribution of de novo urea genesis to the rebound was estimated from the interdialytic increase in plasma urea concentrations, and was 17 to 24% of the plasma urea rebound during two hours postdialysis. The initial plasma urea rebound could in part result from urea influx to plasma from the enterohepatic recirculation of urea nitrogen. Plasma urea rebound should be taken into account for determination of the amount of dialysis delivered during hemodialysis. 57-13-6 (Urea); Samuelsson O, Aurell M, Knight-Gibson C, Alaupovic P, Attman PO. Apolipoprotein-B-containing lipoproteins and the progression of renal insufficiency. Nephron 1993; 63(3):279-85. Hyperlipidemia is associated with accelerated glomerular sclerosis in experimental renal insufficiency. To investigate whether the dyslipoproteinemia seen in human renal failure also influences the future course of renal insufficiency, we have correlated plasma levels of lipids and apolipoproteins at start of follow-up with the subsequent change in renal function in 34 adult patients with chronic renal disease. Nineteen patients had primary renal disease, and 15 patients had diabetic nephropathy. Except for antihypertensive therapy no specific treatment to modify the progression of the disease was given during the follow-up. The rate of progression was determined by repeated measurements of the glomerular filtration rate (GFR). The time of follow-up ranged from 12 to 91 months with an average of 39.7 +/- 16.7 months. The mean initial GFR was 34.7 +/- 13.9 ml/min x 1.73 m2 body surface area and the average decline in renal function was -0.27 +/- 0.26 ml/min/month. The entry levels of triglycerides (TG; p = 0.04), very-low-density lipoprotein cholesterol (p = 0.03), apolipoprotein-B (ApoB; p = 0.008) and systolic blood pressure (SBP; p = 0.04) were significantly correlated with the rate of progression. Among lipoprotein variables, ApoB showed the strongest correlation with the decline in GFR. Patients with a progressive course of their disease also tended to have initially higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (NS), whereas the initial plasma concentration of high-density lipoprotein cholesterol did not show an association with the progression of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) 0 (Apolipoproteins B); 0 (Lipoproteins); Tarkowski A, Andersson-Gare B, Aurell M. Use of anti-thymocyte globulin in the management of refractory systemic autoimmune diseases. Scand J Rheumatol 1993; 22(6):261-6. The purpose of our pilot study was to evaluate the short-and long-term efficacy of T-lymphocyte depletion in the management of patients with refractory, systemic autoimmune diseases. Nine patients with severe, therapy-resistant autoimmune diseases were subjected to T-cell depletion procedure using polyclonal anti-T-cell antibodies combined with peroral administration of azathioprine and/or cyclosporine. The proband group consisted of 4 patients with systemic lupus erythematosus, 3 with progressive systemic sclerosis, and 2 with rheumatoid arthritis. Administration of polyclonal anti-T-cell antibodies was performed at a single occasion via a central venous catheter during 9-10 days. Immunological analyses of T-cell phenotypes and function and assessment of organ function (kidneys, lungs, bone-marrow) has been performed prospectively in all the patients studied. This treatment resulted in prompt and long-lasting (mean follow-up time: 25.6 months) improvement of autoimmune hemolytic anemia, glomerulonephritis, lung fibrosis, skin and joint involvements in the majority of cases. Adverse effects of this treatment included two episodes of infection (E. coli and Cytomegalovirus) and three cases of serum sickness, and were all easily managed. We suggest that this treatment modality adopted from transplant rejection therapy could be employed in cases of severe autoimmune diseases unresponsive to regular immunosuppressive treatment. 0 (Antilymphocyte Serum); Aurell M, Bjorck S. Mechanisms of progression of diabetic nephropathy. Conclusions based on clinical observations. Contrib Nephrol 1992; 98:125-32. 0 (Dietary Proteins); 57-88-5 (Cholesterol); Aurell M, Bjorck S. Determinants of progressive renal disease in diabetes mellitus. Kidney Int Suppl 1992; 36:S38-42. The prognosis for the patient with diabetic nephropathy has improved considerably during the last decade. This is due to identification and treatment of different risk factors. Elevated blood pressure has turned out to be a major risk factor in established diabetic nephropathy. The impact of metabolic control has also been demonstrated. Lipid abnormalities have recently been identified as a possible factor that accelerates loss of renal function. The role of renal hemodynamic alterations is probably also important. Their contribution can indirectly be assessed by studying the effects of pharmacologic therapy. Angiotension converting enzyme inhibitors reduce proteinuria by a mechanism independent of systemic blood pressure and there is suggestive evidence that they preserve renal function to a greater degree than other antihypertensive agents. 0 (Dietary Proteins); Aurell M, Boijsen M. Kontrastmedelsnefropati--kommentar om riskfaktorer och prevention. Lakartidningen 1992; 89(24):2180. English title: "Nephropathy induced by a contrast medium--comments on risk factors and prevention" 0 (Contrast Media); Bardelli M, Jensen G, Volkmann R, Aurell M. Non-invasive ultrasound assessment of renal artery stenosis by means of the Gosling pulsatility index. J Hypertens 1992; 10(9):985-9. OBJECTIVE: To gauge the effectiveness of a new Doppler test for renal artery stenosis (RAS), based on the pulsatility index of the blood flow velocity spectrum within several interlobar arteries of both kidneys. METHODS: Twenty normotensive volunteers and 49 hypertensive patients were investigated with ultrasound. Patients with angiographic signs of RAS underwent bilateral renal vein catheterization for renin measurement. Significant RAS was assumed if lateralization of renal vein renin to the stenotic side was proven. RESULTS: The pulsatility index was higher in the hypertensives without RAS than in normal volunteers. Side differences between both kidneys were within methodological variations with the exception of one case, in whom side difference was > 0.12. The pulsatility index was lower in kidneys with significant RAS than in kidneys without RAS. In most patients with significant unilateral RAS the side difference was < 0.12. In the other patients with a low pulsatility index and a side difference < 0.12 RAS was found to be bilateral upon angiography. Doppler signals were absent in all kidneys with renal occlusion. CONCLUSIONS: A side difference of > or = 0.12 predicts unilateral RAS, whereas the absence of parenchymal Doppler signals indicate occlusive RAS. A low pulsatility index combined with normal side difference may, in hypertensive patients, indicate bilateral RAS. Renovascular hypertension was correctly diagnosed in 84% of the patients and the presence of RAS in 94%. EC 3.4.23.15 (Renin); Bardelli M, Jensen G, Volkmann R, Caidahl K, Aurell M. Experimental variations in renovascular resistance in normal man as detected by means of ultrasound. Eur J Clin Invest 1992; 22(9):619-24. The pulsatility index (PI) of blood flow velocities has been reported to vary with changes in peripheral vascular resistance. Since blood flow velocities can easily be detected with the Echo-Color-Doppler technique in interlobar arteries of normally positioned kidneys, we tried in six healthy volunteers to estimate pharmacological induced variations in renal plasma flow (RPF) and renovascular resistance (RVR) by means of PI measurements. In this study no significant correlation between the absolute values of PI and RVR was found. In order to correct PI for different blood pressure-inputs to the renal artery, PI was divided by the pulsatility of the systemic arterial pressure, i.e. the 'blood pressure index' [BPI = (SAD-DAP)/MAP)], resulting in the 'velocity blood-pressure index' (VBI = PI/BPI), which was significantly correlated with RVR (r = 0.54, P less than 0.01). The pharmacological induced changes of RPF and RVR (delta RPF, delta RVR) were also correlated to the respective changes of PI and VBI (delta PI, delta VBI), with the highest significance when delta VBI was plotted against delta RVR (r = 0.83, P less than 0.0001). VBI, i.e. the pulsatility index of blood flow velocities as corrected for the pulsatility of the driving force, may be a tool for noninvasive assessment of changes in RVR and thereby of importance for the diagnosis and follow-up of renovascular diseases. 11128-99-7 (Angiotensin II); 61-78-9 (p-Aminohippuric Acid); 84680-54-6 (Enalaprilat); Bjorck S, Mulec H, Johnsen SA, Norden G, Aurell M. Renal protective effect of enalapril in diabetic nephropathy. BMJ 1992; 304(6823):339-43. OBJECTIVE--To determine whether inhibition of angiotensin converting enzyme can reduce the rate of decline in kidney function more than reducing blood pressure with other antihypertensive treatment. DESIGN--Prospective, open randomised study lasting a mean of 2.2 years in patients with diabetic nephropathy. SETTING--Three outpatient nephrology clinics. PATIENTS--40 patients with insulin dependent diabetes and diabetic nephropathy with reduced renal function. INTERVENTION--Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURE--Rate of decline in glomerular filtration rate measured as chromium-51 edetic acid clearance. RESULTS--Glomerular filtration rate declined a mean of 2.0 (SD 3.2) ml/min/year in the group given enalapril and 5.6 (5.9) ml/min/year in the control group. The mean arterial blood pressure during the study was 102 (5) mm Hg in the patients given enalapril and 103 (5) mm Hg in the patients given metoprolol. Urinary albumin excretion during treatment with enalapril was 60% lower than during treatment with metoprolol. CONCLUSIONS--Enalapril has an antiproteinuric effect independent of the effect on systemic blood pressure. Treatment with enalapril can reduce the rate of decline in kidney function in patients with diabetic nephropathy more than equally effective antihypertensive treatment with metoprolol. This points to a specific renal protective effect of angiotensin converting enzyme inhibitors in diabetic nephropathy. 37350-58-6 (Metoprolol); 75847-73-3 (Enalapril); Dahlof B, Herlitz H, Aurell M, Hansson L. Reversal of cardiovascular structural changes when treating essential hypertension. The importance of the renin-angiotensin-aldosterone system. Am J Hypertens 1992; 5(12 PT 1):900-11. Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system (RAAS) and in hemodynamics in relation to observed changes in cardiovascular structure. We studied previously untreated men (n = 28) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate (> 1-week interval) occasions measured in triplicate. We used intraarterial blood pressure, dye-dilution technique, plethysmography (hands), eye-ground photos, M-mode echocardiography, radio immunoassays, and multiple regression analysis. Patients were randomized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide, following 4 to 6 weeks on placebo. We found that enalapril blocked the plasma angiotensin converting enzyme (ACE) with a secondary increment in plasma renin activity (PRA) and reductions in angiotensin II (AII) and aldosterone. Blood pressure was lowered through a reduction in total peripheral resistance (TPR). Hydrochlorothiazide increased PRA, AII, and aldosterone, and lowered blood pressure mainly through a reduction in cardiac output. Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and hand vasculature as well as in the heart. A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient, in whom little or no reduction in blood pressure occurred. In the stepwise regression analyses, the changes in retinal and hand vascular structure were most strongly related to various changes in the RAAS, explaining 15 to 34% of the variance. For the changes in cardiac structure, the type of therapy (enalapril or hydrochlorothiazide) appeared to be the most important factor, explaining between 29 and 50% of the variance. The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55% of the variance in cardiac structure. It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure. 58-93-5 (Hydrochlorothiazide); 84680-54-6 (Enalaprilat); EC 3.4.15.1 (Peptidyl-Dipeptidase A); EC 3.4.23.15 (Renin); Granerus G, Aurell M, Delin K, Karlberg BE, Lorelius LE. A Swedish view on the diagnosis of renovascular hypertension. J Intern Med 1992; 232(1):15-24. EC 3.4.23.15 (Renin); Jensen G, Bjorck S, Nielsen OJ, Volkmann R, Aurell M. Diagnostic use of renal vein erythropoietin measurements in patients with renal artery stenosis. Nephrol Dial Transplant 1992; 7(5):400-5. The relationship between the renin-angiotensin system and erythropoietin was studied in twenty patients with renal artery stenosis and hypertension. Ten of the patients had a unilaterally activated renin-angiotensin system (group 1), while ten patients had not (group 2). Plasma erythropoietin was simultaneously measured in a brachial artery and both renal veins before and 5 and 30 min after an intravenous injection of 1.25 mg enalaprilat. The mean (+/- SD) arterial erythropoietin concentration was 27.3 +/- 16.8 mU/ml in group 1 and 14.1 +/- 11.3 mU/ml in group 2 patients (P less than 0.05). There was no significant change after enalaprilat i.v. in either group. The venous erythropoietin concentration in plasma from the stenotic kidney did not differ from that of the contralateral kidney. The higher erythropoietin concentration in group 1 patients may be explained by a systemic stimulatory effect of the renin-angiotensin system on erythropoietin production. As no side-differences were found, renal vein as well as peripheral erythropoietin measurements cannot be used as a tool in the diagnosis of the functional significance of a renal artery stenosis. 11096-26-7 (Erythropoietin); 84680-54-6 (Enalaprilat); Widgren BR, Herlitz H, Aurell M, Berglund G, Wikstrand J, Andersson OK. Increased systemic and renal vascular sensitivity to angiotensin II in normotensive men with positive family histories of hypertension. Am J Hypertens 1992; 5(3):167-74. Normotensive young men (mean age 36 years) with positive (PFH) (n = 13) and negative (n = 29) family histories of hypertension were investigated in order to study systemic and renal hemodynamics at baseline conditions and during infusion of low doses (0.1 and 0.5 ng/min/kg) of angiotensin II (AII). The control group with negative family histories of hypertension was subdivided into one group matched for body mass index (n = 15) to subjects with PFH, and one lean control group (n = 14). Baseline blood pressure and sodium intake, measured as urinary excretion, were higher in PFH and in matched controls than in the lean control group. At baseline, renal blood flow (para-aminohippurate clearance) did not differ significantly among the three groups, while glomerular filtration rate (inulin clearance) was higher in PFH than in matched controls. Both doses of angiotensin II infusion increased the blood pressure significantly in PFH. In matched controls a small increase in blood pressure was seen with the highest dose only, while no change in blood pressure was observed in the lean control group. In PFH both doses of AII infusion caused diminished renal blood flow (P less than .01) and increased renal vascular resistance (P less than .001). The two control groups remained unchanged with both AII doses. These results could indicate that normotensive subjects with positive family histories of hypertension are characterized by an increased sensitivity to AII in the systemic and renal circulation as compared with subjects with negative family histories of hypertension. 11128-99-7 (Angiotensin II); 51-41-2 (Norepinephrine); 52-39-1 (Aldosterone); 7440-09-7 (Potassium); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Aurell M. Pa vag mot billig och lattillganglig bestamning av glomerular filtration. Lakartidningen 1991; 88(21):1954 1957. English title: "Towards a cheap and easily available determination of glomerular filtration rate" 0 (Chromium Radioisotopes); 0 (Contrast Media); 60-00-4 (Edetic Acid); Aurell M. Langtidsbehandling med litium. Ugeskr Laeger 1991; 153(10):728. English title: "Prolonged treatment with lithium" 7439-93-2 (Lithium); Friberg P, Volkmann R, Jensen G, Aurell M. Norepinephrine overflow and renin pattern of the individual kidney in patients with unilateral renal artery stenosis. Hypertension 1991; 17(6 PT 2):1003-9. This study was performed to determine divided renal efferent sympathetic nerve activity from kidneys in seven patients with renin-positive, unilateral renal artery stenosis before and 30 minutes after an acute intravenous dose of 1.25 mg enalaprilat. Renal norepinephrine release was calculated from split renal plasma flow, venoarterial plasma concentration gradients across the kidney, and the fractional extraction of tritiated norepinephrine. All patients had unilateral renin secretion, the affected kidney increasing its plasma renin activity gradient 1.7-fold, whereas no statistically significant change was noted on the contralateral side in response to enalaprilat. Total norepinephrine release to plasma and norepinephrine plasma clearance (assessed by isotope dilution) were similar before and after administration of enalaprilat (approximately 400 ng/min and 1.0 l/min), despite a 26% fall in mean arterial pressure (from 125 mm Hg, p less than 0.01). Heart rate remained unchanged. After enalaprilat, norepinephrine venoarterial difference increased in the renin-secreting kidney (from 264 to 396, SED = 57 pg/ml, p less than 0.05), whereas it increased only slightly in the contralateral kidney (from 149 to 256, SED = 72 pg/ml, NS). Tritiated norepinephrine extraction fell approximately 25% (p less than 0.01) in both kidneys. Thus, renal norepinephrine spillover increased from 49 to 62, SED = 9 ng/min (NS) and from 81 to 129, SED = 17 ng/min (p less than 0.05) from the affected and the contralateral kidney, respectively. Hence, in this relatively small study in patients with renovascular hypertension, no evidence for increased renal nerve activity could be observed in the affected kidney, despite its marked renin production.(ABSTRACT TRUNCATED AT 250 WORDS) 0 (Angiotensin-Converting Enzyme Inhibitors); 51-41-2 (Norepinephrine); 84680-54-6 (Enalaprilat); EC 3.4.23.15 (Renin); Krotkiewski M, Aurell M, Holm G, Grimby G, Szczepanik J. Effects of a sodium-potassium ion-exchanging seaweed preparation in mild hypertension. Am J Hypertens 1991; 4(6):483-8. A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty-two middle-aged patients with mild hypertension were given a potassium loaded ion-exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium-sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension. 0 (Carrier Proteins); 0 (Triglycerides); 0 (sodium, potassium, chloride-cotransporter); 57-88-5 (Cholesterol); 7439-89-6 (Iron); 7440-09-7 (Potassium); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Aurell M, Herlitz H. Langtidsbehandling med litium ger biverkningar. Lakartidningen 1990; 87(34):2560. English title: "Long-term lithium treatment has side effects" 7439-93-2 (Lithium); Aurell M, Samuelsson O, Attman PO. Prognostic impact of ACE inhibition in systemic lupus erythematosus, diabetes mellitus and chronic glomerulonephritis. Contrib Nephrol 1990; 81:248-54. 0 (Angiotensin-Converting Enzyme Inhibitors); Bjorck S, Aurell M. Diabetes mellitus, the renin-angiotensin system, and angiotensin-converting enzyme inhibition. Nephron 1990; 55 Suppl 1:10-20. Many traditional antihypertensive drugs are linked to various effects that may cause concern in the hypertensive diabetic patient. The favorable tolerability of angiotensin-converting enzyme (ACE) inhibitors in essential hypertension makes it likely that they will be well tolerated when used in diabetic patients. Data from ongoing studies support the theory that ACE inhibitors lower blood pressure to the same extent in hypertensive diabetics as in patients with essential hypertension. ACE inhibitors do not seem to affect glucose homeostasis adversely; they may even improve glucose tolerance to a small degree. The renal effects of ACE inhibitors in animal experiments suggest a renal-protective effect that can make them especially valuable. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Receptors, Angiotensin); 11128-99-7 (Angiotensin II); 52-39-1 (Aldosterone); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Bjorck S, Aurell M, Bresater LE, Herlitz H, Welin L, Wikstrand J. Renal sensitivity to angiotensin II in type 1 diabetes. Scand J Urol Nephrol 1990; 24(4):267-73. The role of the renin angiotensin system for the regulation of kidney function in diabetes mellitus is uncertain. Results from studies in diabetic animals suggest that a reduced activity in this system contributes to the renal hyperperfusion and hyperfiltration in diabetes. The renal sensitivity to angiotensin II in diabetic patients is also unknown. Changes in renal hemodynamics were measured after infusion of two low doses of angiotensin II in ten young type 1 diabetic patients without complications and in ten healthy controls. The renin and angiotensin II levels were found to be the same in both groups. The baseline glomerular filtration rate was higher in the diabetics. During the highest angiotensin II dose, the 51Cr-EDTA and PAH clearance decreased 14 +/- 15 and 157 +/- 118 ml/min in the diabetics and 14 +/- 15 and 146 +/- 109 in the controls respectively. The changes in blood pressure and renal vascular resistance or sodium excretion did not differ between the groups. A malfunction of the renin angiotensin system is thus unlikely as a cause of the glomerular hyperfiltration in type 1 diabetes. 11128-99-7 (Angiotensin II); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Bjorck S, Mulec H, Johnsen SA, Nyberg G, Aurell M. Contrasting effects of enalapril and metoprolol on proteinuria in diabetic nephropathy. BMJ 1990; 300(6729):904-7. OBJECTIVE--To assess whether angiotensin converting enzyme inhibition reduces proteinuria in diabetic nephropathy more than blood pressure reduction with other antihypertensive treatment. DESIGN--Prospective, open randomised study lasting eight weeks in patients with diabetic nephropathy. SETTING--Outpatient nephrology clinics. PATIENTS--40 Patients with type I diabetes and diabetic nephropathy with reduced renal function. INTERVENTION--Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURES--Arterial blood pressure and urinary excretion of albumin and protein. RESULTS--Arterial blood pressure after eight weeks was 135/82 (SD 13/7) mm Hg in the group given enalapril and 136/86 (16/12) mm Hg in the group given metoprolol. Proteinuria and albuminuria were similar in both groups before randomisation. After eight weeks' treatment, the geometric mean albumin excretion was 0.7 (95% confidence interval 0.5 to 1.2) g/24 h in the patients given enalapril and 1.6 (1.1 to 2.5) g/24 h in the patients given metoprolol (p less than 0.02). The proteinuria was 1.1 (0.7 to 1.7) and 2.4 (1.6 to 3.6) g/24 h respectively (p less than 0.02). CONCLUSIONS--Antihypertensive treatment with enalapril reduced proteinuria in patients with diabetic nephropathy more than an equally effective antihypertensive treatment with metoprolol. This points to a specific antiproteinuric effect of the angiotensin converting enzyme inhibitor independent of the effect on systemic blood pressure. 37350-58-6 (Metoprolol); 75847-73-3 (Enalapril); Herlitz H, Andersson OK, Jonsson O, Wysocki M, Persson B, Aurell M. Effect of acute vascular fluid volume expansion on erythrocyte sodium transport in essential hypertension. Scand J Clin Lab Invest 1990; 50(2):123-8. Evidence exists that volume expansion is associated with the appearance of a circulating sodium transport inhibitor. We have evaluated intra-arterial blood pressure (BP), central venous pressure (CVP), plasma renin activity (PRA), intraerythrocyte sodium content, erythrocyte sodium influx and rate constant of sodium efflux in 10 untreated primary hypertensive men (WHO stages I and II). The investigations were done during baseline conditions and after rapid intravenous infusion of 1 litre of saline (0.9% NaCl solution) over 15-20 min. Volume expansion caused an increase in CVP by 6.0 +/- 0.5 cmH2O (p less than 0.01), while BP only exhibited a slight increase. No significant changes in intraerythrocyte sodium content, sodium influx, sodium efflux rate constant or PRA were found after volume expansion compared to baseline. All patients with low normal PRA experienced a decrease in sodium efflux rate constant after volume expansion. We found a positive correlation between baseline PRA and change in sodium efflux rate constant after volume expansion (r = 0.62, p less than 0.05). At baseline the relationship between PRA and intraerythrocyte sodium content nearly reached statistical significance (r = 0.63, p = 0.054). These results may indicate that acute volume expansion influences the release of a circulating factor, modulating sodium transport in low-renin hypertension. 7440-23-5 (Sodium); 7647-14-5 (Sodium Chloride); EC 3.4.23.15 (Renin); Herlitz H, Granerus G, Aurell M. Long-term effects of felodipine on blood pressure and renal hemodynamics in severe hypertension. J Cardiovasc Pharmacol 1990; 15 Suppl 4:S100-2. Felodipine, a dihydropyridine calcium antagonist, was used to treat eight patients with severe uncontrolled hypertension: five had essential hypertension, two had renovascular disease, and one chronic pyelonephritis. Mean blood pressure (BP) was 221 +/- 14/120 +/- 4 mm Hg despite treatment with three or more antihypertensive drugs. All patients experienced an immediate and pronounced lowering of BP after adding felodipine, which persisted during long-term treatment in combination with previous medication except for vasodilating drugs. In all cases, an increase in glomerular filtration rate (51Cr-EDTA clearance) after 6 and 12 months of felodipine treatment was seen (59 +/- 10 to 63 +/- 7 and 70 +/- 6 ml/min, respectively, p less than 0.05). Renal plasma flow (PAH clearance) exhibited only a slight increase (315 +/- 68 to 340 +/- 63 and 314 +/- 69 ml/min), giving a nonsignificant rise in filtration fraction (18 +/- 1 to 21 +/- 1 and 20 +/- 1%, respectively). It is concluded that felodipine decreases BP dramatically in patients with previously refractory hypertension and that the drug causes an improved renal function in these patients. 72509-76-3 (Felodipine); Herlitz H, Hjemdahl P, Delin K, Granerus G, Aurell M. Plasma noradrenaline and dopamine in renin-mediated hypertension. Clin Physiol 1990; 10(1):27-36. Noradrenaline (NA) and dopamine (DA) have opposite effects on the kidney; NA causes vasoconstriction and increased sodium reabsorption while DA promotes vasodilation and natriuresis. In 15 patients investigated for renin-mediated hypertension measurements of plasma renin activity (PRA), NA and DA concentrations were made in arterial and renal venous blood from both kidneys before and after acute stimulation of renin release by i.v. dihydralazine. Nine patients had unilateral renin secretion and were classified as renin-positive, while the remaining six patients were renin-negative. Renin-positive patients had higher arterial and renal venous PRA, NA and DA levels than the negative ones. In the renin-positive group V-A differences for NA and DA were present on both sides despite unilateral secretion of renin. NA but not DA levels were higher in the renin-secreting kidney, which can partly be explained by the reduced plasma flow to the involved kidney. After dihydralazine the arterial NA and DA rose similarly in renin-positive and renin-negative patients, while PRA rose only in the renin-positive cases. In the renin-positive patients where stimulation of renin secretion caused a marked increase of the PRA gradient on the affected side only, renal gradients for NA and DA increased bilaterally. The increase in DA was more pronounced than that of NA yielding a rise in DA/NA ratio on the affected side. Arterial PRA was positively correlated to the plasma concentrations of NA and DA. V-A differences for PRA and NA or DA were positively correlated on the involved renin-secreting side. In summary, patients with renin-dependent hypertension have elevated plasma NA and DA concentrations. Stimulation of renin release by dihydralazine increases the DA/NA ratio in arterial and renal venous blood indicating release of 'precursor dopamine' from noradrenergic fibres and/or activation of dopaminergic nerves. There seems to be a relationship between renal nerve activity and renin release in renin-dependent hypertension. 51-41-2 (Norepinephrine); 51-43-4 (Epinephrine); 51-61-6 (Dopamine); EC 3.4.23.15 (Renin); Andersson OK, Persson B, Hedner T, Aurell M, Wysocki M. Blood pressure control and haemodynamic adaptation with the dihydropyridine calcium antagonist isradipine: a controlled study in middle-aged hypertensive men. J Hypertens 1989; 7(6):465-9. Twenty-three middle-aged men (59 +/- 2 years) with sustained, essential hypertension (WHO Stage II) and with diastolic blood pressure exceeding 100 mmHg during a run-in placebo month were included in a trial designed to assess the clinical and haemodynamic effects of isradipine, a novel dihydropyridine calcium antagonist. The study was double-blind with a placebo-controlled crossover design. Isradipine as monotherapy was titrated in three, 3-week periods in doses of 2.5, 5 and 7.5 mg twice daily, or as apparently identical placebo capsules. A 3-week placebo wash-out period separated the two phases of the study. Clinical characteristics were followed during each treatment phase and an invasive haemodynamic examination was performed on the last day of the final active or placebo dose. In the haemodynamic investigation, cardiac output was measured using a dye-dilution technique and blood pressure via a catheter in the brachial artery. Plasma renin activity (PRA) was assessed by radio-immunoassay of generated angiotensin I and arterial noradrenaline concentrations using high-performance liquid chromatography (HPLC). Baroreceptor sensitivity was calculated from R-R intervals of the ECG and beat-to-beat systolic blood pressure during increasing bolus injections of phenylephrine. During optimal therapy with isradipine (7.5 mg twice daily), highly significant decreases in supine systolic (from 174 +/- 4 to 154 +/- 3 mmHg) and diastolic blood pressures (from 104 +/- 2 to 91 +/- 1 mmHg) were observed. Heart rate was unchanged (79 +/- 3 versus 81 +/- 2 beats/min) during chronic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) 0 (Calcium Channel Blockers); 0 (Pyridines); 51-41-2 (Norepinephrine); 75695-93-1 (Isradipine); EC 3.4.23.15 (Renin); Edgar B, Regardh CG, Attman PO, Aurell M, Herlitz H, Johnsson G. Pharmacokinetics of felodipine in patients with impaired renal function. Br J Clin Pharmacol 1989; 27(1):67-74. The pharmacokinetics of felodipine and its effects on blood pressure and heart rate were studied in eight male patients aged between 28 and 57 years with a glomerular filtration rate, GFR, between 8 and 68 ml min-1, following single i.v. and oral administration. 2. Clearance, Cmax, AUC, Vss and V, of felodipine were unaffected by the renal disease. The metabolite excretion (14C-labelled) was slower than in healthy subjects. Initial renal clearance of these metabolites correlated with individual GFR values. The total amount of the dose excreted in the urine was also decreased. 0 (Calcium Channel Blockers); 39562-70-4 (Nitrendipine); 72509-76-3 (Felodipine); Keane WF, Anderson S, Aurell M, de Zeeuw D, Narins RG, Povar G. Angiotensin converting enzyme inhibitors and progressive renal insufficiency. Current experience and future directions. Ann Intern Med 1989; 111(6):503-16. STUDY OBJECTIVE: To review the rationale for using angiotensin converting enzyme (ACE) inhibitors in progressive renal disease, and to evaluate the experience with these agents in patients with hypertension and renal insufficiency. DATA IDENTIFICATION: Experimental and clinical studies published from January 1977 to November 1988 were identified by searching the literature and by extensive hand searching of bibliographies of identified articles. STUDY SELECTION: Experimental studies of glomerular function during therapy with ACE inhibitors or other antihypertensive regimens were reviewed. Series using ACE inhibitors for treating hypertensive patients with renal disease were evaluated and reports of adverse events were studied. RESULTS OF DATA SYNTHESIS: Experimentally, ACE inhibitors seem to decrease glomerular injury by reducing both systemic and glomerular hypertension. Clinically, ACE inhibitors reduce systemic blood pressure in hypertensive patients with diabetic and nondiabetic renal disease without causing dramatic changes in glomerular filtration rate or renal blood flow. Most studies of nondiabetic renal insufficiency suggest that proteinuria is reduced in most patients. However, no long-term controlled study on the effect of ACE inhibitors on the progression rate of nondiabetic renal disease has been completed. ACE inhibitors have not yet been approved by the Food and Drug Administration (FDA) for treating or preventing progressive renal disease. Such use would therefore be considered "innovative" therapy. CONCLUSIONS: ACE inhibitors are tolerated by azotemic patients, although transient reductions in renal function can occur. Patients with bilateral renal insufficiency or low cardiac output are at increased risk for developing reversible acute renal insufficiency. Hyperkalemia may occur, particularly in patients with diabetes or severe renal insufficiency. In many patients with renal disease, ACE inhibitors dramatically reduce proteinuria, but whether they also reduce the rate of progression of renal disease remains unproved. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antihypertensive Agents); Persson B, Andersson OK, Wysocki M, Hedner T, Aurell M. Renal and hemodynamic effects of isradipine in essential hypertension. Am J Med 1989; 86(4A):60-4. Twenty-three men with essential hypertension participated in a double-blind placebo-controlled study with a crossover design to evaluate the long-term (nine weeks) effects of isradipine on central and renal hemodynamics. Isradipine as monotherapy was titrated from 2.5 to 5 and then to 7.5 mg twice daily. At the end of the crossover periods, cardiac output (dye-dilution) and intraarterial blood pressure were assessed. Compared with placebo, isradipine reduced ambulatory blood pressure from 174/104 to 154/91 (p less than 0.001), whereas the heart rate was unchanged. The reduction of blood pressure was entirely due to a reduction (36 percent; p less than 0.001) of the peripheral resistance. The baroreceptor sensitivity did not change (RR intervals during infusion of phenylephrine) but, with isradipine, the setpoint was shifted to lower blood pressure levels. Renal plasma flow (para-amino hippurate clearance) increased (465 versus 391 ml/minute; p less than 0.05), but glomerular filtration rate ([51Cr]ethylenediaminetetraacetic acid clearance) did not change. Hence, the filtration fraction decreased. With isradipine, there was a post-dose increase in natriuresis (0.45 to 0.34 mmol/minute; p = 0.06). Side effects were mild. 0 (Antihypertensive Agents); 0 (Calcium Channel Blockers); 0 (Placebos); 0 (Pyridines); 75695-93-1 (Isradipine); Aurell M. Aspects of the role of intraglomerular pressure as a cause of progressive renal damage. Drugs 1988; 35 Suppl 5:42-7. Renal damage in hypertension was thought to be a result of excessive renal arteriolar constriction leading to ischaemia and nephron damage. However, more recent studies have shown that in animal models the aetiology is one of increased intraglomerular pressure, and there is strong evidence that this is also the case in patients with essential hypertension. The problem is therefore one of inadequate constriction of afferent arterioles allowing increased systemic pressure to be transmitted to the glomerular capillaries. Since angiotensin II preferentially constricts the efferent arterioles, and since hypertensive patients have increased renovascular sensitivity to angiotensin II, this may explain why angiotensin-converting enzyme inhibitors are the only drugs which actually lower intraglomerular pressure and why they reduce renal damage in hypertensive disease. Human; Hypertension, Renal/complications/physiopathology; Kidney Diseases/etiology; Kidney Glomerulus/physiopathology; Aurell M. The kidney as a target organ in antihypertensive treatment. Scand J Urol Nephrol Suppl 1988; 108:7-12. 0 (Antihypertensive Agents); Balldin J, Berggren U, Svennerholm L, Kjellbo H, Lindstedt G, Aurell M. Reduced glomerular filtration rate in a lithium-treated bipolar patient with primary hypothyroidism--reversal by levothyroxine. Clin Nephrol 1988; 29(3):160-1. 7439-93-2 (Lithium); 7488-70-2 (Thyroxine); Bjorck S, Svalander CT, Aurell M. Acute renal failure after analgesic drugs including paracetamol (acetaminophen). Nephron 1988; 49(1):45-53. Seven patients with acute renal failure after ingestion of analgesic drug combinations including paracetamol were seen. They presented with oliguric renal failure and restitution of renal function was complete. Only 2 patients had severe liver damage and 2 patients had no signs of liver abnormality. Renal biopsies, studied by light and electron microscopy, in 3 patients showed focal tubular epithelial cell necrosis. Focal vascular damage, predominantly of endothelial cells, was also present in all specimens. This vascular injury was found in various locations in the kidney, including the glomerular and peritubular capillaries and small arterioles. This suggests that microvascular damage is an important mechanism for the renal injury after analgesic drugs. 0 (Analgesics); 103-90-2 (Acetaminophen); Boijsen M, Granerus G, Jacobsson L, Bjorneld L, Aurell M, Tylen U. Glomerular filtration rate estimated after multiple injections of contrast medium during angiography. Acta Radiol 1988; 29(6):669-74. In twenty-six patients referred for angiography, clearance of contrast medium was determined with x-ray fluorescence analysis after multiple injections of contrast medium. A formula for correction of the injected amount, which takes into consideration the different times of contrast medium injections, approximating the total injected amount into one injection, was used. A single injection clearance of 51Cr-EDTA was determined at the same time. The results showed a good correlation between the clearance of contrast medium after multiple injections and the 51Cr-EDTA clearance after a single injection (r = 0.945). The correlation between contrast medium clearance calculated without correction for the different injection times, and 51Cr-EDTA clearance was the same (r = 0.946), due to short angiography time and rather low clearance values in our patients. It is concluded that total plasma clearance of contrast medium can easily be estimated after multiple injections. In this way patients with a risk of developing post-angiographic renal failure can be found. 0 (Chromium Radioisotopes); 0 (Contrast Media); 60-00-4 (Edetic Acid); Bratt CG, Aurell M, Jonsson O, Nilsson S. Long-term followup of maximum concentrating ability and glomerular filtration rate in adult obstructed kidneys after pyeloplasty. J Urol 1988; 140(2):273-6. We investigated 34 patients with obstructed kidneys preoperatively and 8 to 10 years postoperatively concerning the separate glomerular filtration rate and maximum concentration ability. The mean glomerular filtration rate for the obstructed kidneys was approximately 10 per cent lower compared to that for the contralateral kidneys preoperatively and at followup. Although the mean value for obstructed kidneys was not improved at followup, kidneys with a decreased glomerular filtration rate preoperatively improved significantly after pyeloplasty. The maximum concentration ability was low preoperatively for the obstructed kidneys compared to the contralateral kidneys. The lowest maximum concentration ability was found in patients with a history of repeated upper urinary tract infections. At followup marked improvement was noted, which was most obvious for kidneys with severely reduced concentration ability preoperatively. However, the restoration was not total. There was a positive correlation between the improvement in glomerular filtration rate and improvement in maximum concentration ability. Adult; Aged; Female; Follow-Up Studies; Glomerular Filtration Rate; Human; Hydronephrosis/physiopathology/surgery; Kidney Concentrating Ability; Male; Middle Age; Postoperative Period; Ureteral Obstruction/surgery; Darnfors C, Wahlstrom J, Jensen G, Bjursell G, Aurell M. Diagnostik av adult form av polycystiska njurar med hjalp av genetisk kopplingsanalys. Lakartidningen 1988; 85(24):2193-4. English title: "Diagnosis of adult type of polycystic kidney by means of genetic linkage analysis" 9007-49-2 (DNA); Herlitz H, Fagerberg B, Jonsson O, Hedner T, Andersson OK, Aurell M. Effects of sodium restriction and energy reduction on erythrocyte sodium transport in obese hypertensive men. Ann Clin Res 1988; 20 Suppl 48:61-5. Twelve moderately obese middle-aged male out-patients with untreated mild hypertension reduced their sodium intake by about 120 mmol/day during 4-6 weeks. The low sodium diet period was followed by a period of energy reduction as well as sodium restriction for 15 weeks. Mean body mass was then reduced by 7.5 +/- 1.0 kg. Intraerythrocyte sodium (IeNa), sodium influx (Na-influx) and sodium efflux rate constant (Na-efflux rate), were measured before intervention, during salt restriction and during salt and energy restriction. Plasma renin activity (PRA) and urinary excretion of aldosterone (U-Aldo) and noradrenaline (U-NA) were also determined during the three observation periods. During sodium restriction there was a significant increase in PRA and U-Aldo, but no change was seen in IeNa, Na-influx or Na-efflux rate constant. During sodium restriction there was a significant positive correlation between PRA and both Na-influx and Na-efflux rate constant. When energy reduction was combined with sodium restriction, PRA and U-NA both diminished significantly. Na-influx and Na-efflux rate also exhibited a significant decrease while IeNa did not change. Sodium restriction caused a significant fall in mean arterial blood pressure and a tendency to a further decrease was seen when energy intake was also reduced. No significant correlation could be found between the fall in blood pressure and changes in cellular sodium transport. These data indicate that the renin-angiotensin-aldosterone system and sympathetic activity influence the regulation of erythrocyte sodium turnover during sodium and energy restriction in obese hypertensive men. 7440-23-5 (Sodium); Herlitz H, Nyberg G, Granerus G, Bjorck S, Aurell M. Effects of felodipine in patients with refractory hypertension and progressive renal disease. Scand J Urol Nephrol Suppl 1988; 108:31-4. 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Calcium Channel Blockers); 39562-70-4 (Nitrendipine); 72509-76-3 (Felodipine); Ljungman S, Aurell M, Hartford M, Wikstrand J, Berglund G. Renal function before and after withdrawal of long term antihypertensive treatment in primary hypertension. Drugs 1988; 35 Suppl 5:55-8. Glomerular filtration rate (GFR) and renal plasma flow (inulin and para-aminohippurate clearance) were measured in a random sample of 17 normotensive and 20 untreated patients with primary hypertension. At the 7-year follow-up, 19 patients were on metoprolol (as the sole drug or in combination with either hydrochlorothiazide or hydralazine) and 1 patient was on hydrochlorothiazide. They were re-examined after withdrawal of treatment and return of hypertension. At the 7-year follow-up GFR was more reduced in the hypertensive (-17%) than in the normotensive group (-9%). The percentage decrease in renal blood flow was the same in both groups. No significant renal function changes appeared after withdrawal of treatment. In conclusion, there was a slightly greater deterioration in GFR in the hypertensive patients after long term treatment with metoprolol than can be explained by normal ageing. 0 (Antihypertensive Agents); Mathillas O, Attman PO, Aurell M, Brynger H. Glomerular filtration rate, hypertension and proteinuria after renal ablation: a long-term follow-up study in kidney donors. Scand J Urol Nephrol Suppl 1988; 108:49-55. 0 (Dietary Proteins); Rudin A, Aurell M, Wilske J. Low urinary calcium excretion in Bartter's syndrome. Scand J Urol Nephrol 1988; 22(1):35-9. The urinary calcium excretion has been determined in 19 patients with Bartter's syndrome and found to be significantly lower than the calcium excretion in 92 healthy subjects (1.16 +/- 0.82 vs. 4.36 +/- 2.71 mmol/24 h, p less than 0.001). There were no differences in height, weight, glomerular filtration rate, urinary sodium excretion or serum calcium concentration between the patients and the control subjects to account for the disparity in calcium excretion. In the patients, the concentrations for ionized calcium, PTH, 25-OH vitamin D and 1,25-(OH)2 vitamin D were normal. A low urinary calcium excretion appears to be a characteristic feature of Bartter's syndrome. The cause remains unexplained. 7439-95-4 (Magnesium); 7440-23-5 (Sodium); 7440-70-2 (Calcium); Andersson OK, Persson B, Wysocki M, Berglund G, Towle AC, Aurell M et al. Significant relationship between renin suppression and atrial natriuretic peptide (alpha-hANP) during volume loading in hypertensive men. Acta Med Scand 1987; 221(2):137-42. We have studied eight men with moderate hypertension to determine the atrial natriuretic peptide (alpha-hANP) response to acute volume expansion. Rapid infusion of 1,000 ml 0.9% saline (10-20 min) caused an increase in central venous pressure (4.7 +/- 1.6 cmH2O) while blood pressure and pulse pressure (arterial baroreceptor load) did not change. Stroke volume and heart rate were not affected by the volume load but plasma renin activity (PRA) was significantly suppressed (from 0.83 +/- 0.14 to 0.68 +/- 0.34 microgram AI I/ml-h; p less than 0.01). A significant hemodilution was also observed. Renal sodium excretion was significantly increased. Arterial alpha-hANP increased significantly from 21.1 +/- 6.1 to 30.5 +/- 4.0 pmol/l (p less than 0.02) during volume expansion. There was a significant correlation between corrected plasma volume increase (urine volume subtracted from the infused volume) and alpha-hANP plasma elevation (r = 0.78; p less than 0.05). There was also a significant negative correlation between changes alpha-hANP and PRA (r = -0.78, p less than 0.05). We conclude that only moderate volume loading in human hypertensives is a mechanism for increase in plasma alpha-hANP levels. The significant negative correlation between changes in alpha-hANP and PRA suggests that alpha-hANP may be the humoral factor at least partly responsible for suppression of renin in hypertensive man. Since increased fluid volume also affects sympathetic renal efferents as well as vasopressin secretion, our observed relationship between volume load and renin may well be related also to such mechanisms. 85637-73-6 (Atrial Natriuretic Factor); EC 3.4.23.15 (Renin); Aurell M, Delin K, Herlitz H, Ljungman S, Witte PU, Irmisch R. Pharmacokinetics and pharmacodynamics of ramipril in renal failure. Am J Cardiol 1987; 59(10):65D-9D. The pharmacokinetics and pharmacodynamics of the novel angiotensin converting enzyme (ACE) inhibitor ramipril were studied in 6 patients with a glomerular filtration rate of less than 20 ml/min/1.73 m2 of body surface area. A single oral dose of 5 mg was given and serum concentrations of the compound and its diacid, the active metabolite (ramiprilat), as well as ACE activity, blood pressure and pulse rate were monitored for 28 days. The original compound reached peak serum concentrations of 42.8 +/- 26.5 ng/ml about 1 hour after dosing and was completely eliminated from the serum after 24 hours. Ramiprilat reached peak values of 14.4 +/- 11.6 ng/ml after about 6 hours. In contrast with the parent compound, low concentrations of ramiprilat were still detected in the serum after 28 days. ACE activity decreased to approximately 5% of baseline values, remained low for the next 48 hours, then increased slowly thereafter but reached only 84.5% of initial values after 28 days. Blood pressure decreased significantly and remained low for 24 hours after dosing. The drug was well tolerated in all patients. It is concluded that a single 5 mg dose of ramipril was effective in inhibiting plasma ACE activity and lowering blood pressure in patients with renal failure. There was a slower decline in ramiprilat concentrations compared with subjects with normal renal function. 0 (Bicyclo Compounds); 0 (Bridged Compounds); 87333-19-5 (Ramipril); EC 3.4.15.1 (Peptidyl-Dipeptidase A); Dahlof B, Andren L, Eggertsen R, Jern S, Svensson A, Sievert A et al. Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension. J Cardiovasc Pharmacol 1987; 10 Suppl 10:S102-4. Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control. 0 (Calcium Channel Blockers); 0 (Oxadiazoles); 13523-86-9 (Pindolol); 7440-70-2 (Calcium); 75695-93-1 (Isradipine); Edgar B, Aurell M, Johnsson G, Regardh CG, Shansky C. Effects of impaired renal function on the pharmacokinetics of felodipine. Drugs 1987; 34 Suppl 3:31-2. 0 (Antihypertensive Agents); 39562-70-4 (Nitrendipine); 72509-76-3 (Felodipine); Herlitz H, Bjorck S, Nyberg G, Granerus G, Aurell M. Clinical evaluation of felodipine in patients with refractory hypertension. Drugs 1987; 34 Suppl 3:151-5. The calcium antagonist, felodipine, was used to treat 21 patients with severe uncontrolled hypertension: 13 had renoparenchymatous hypertension, 5 essential hypertension and 3 renovascular hypertension. Mean arterial blood pressure of patients was 195 +/- 8/122 +/- 3mm Hg in spite of treatment with 3 or more antihypertensive drugs. The majority of the patients (n = 17) were treated with an ACE inhibitor. Mean glomerular filtration rate (GFR) for 20 patients was 39 +/- 6 ml/min/1.73m2 body surface area (Cr-EDTA clearance) before felodipine administration. All patients had an immediate blood pressure fall after 5-10mg of felodipine administered orally. This fall persisted when the drug was given 2 or 3 times daily in combination with previous medication except the former vasodilating drugs. 15 patients are on long term treatment with felodipine and their blood pressure after 1 year (n = 14) was 152 +/- 4/89 +/- 2mm Hg. Patients with moderately impaired renal function and no signs of progressive kidney disease (n = 8) improved their GFR significantly after 1 year on felodipine. Six patients stopped felodipine therapy within 3 months (4 because of adverse reactions, 1 died of scleroderma and 1 became normotensive after the start of dialysis treatment). In patients with renoparenchymatous disease and documented progressive deterioration of renal function the addition of felodipine did not prevent a decline in filtration rate but did slow the rate of deterioration (from 9 +/- 2 to 5 +/- 1 ml/min/year).(ABSTRACT TRUNCATED AT 250 WORDS) 0 (Antihypertensive Agents); 39562-70-4 (Nitrendipine); 72509-76-3 (Felodipine); Nyberg G, Norden G, Attman PO, Aurell M, Uddebom G, Lenner RA et al. Diabetic nephropathy: is dietary protein harmful? J Diabet Complications 1987; 1(2):37-40. The suggested harmful effect of dietary protein on renal function in diabetic nephropathy was tested in three groups of insulin-dependent diabetic patients: 1) 10 patients without signs of nephropathy in spite of at least 30 years of diabetes; 2) 11 patients with nephropathy and reduced but stable glomerular filtration rate (GFR) (decline less than 4 ml/min per year [mean 1.8] during the last 2 years); 3) 10 patients with progressive nephropathy with GFR declining by an average of 11 ml/min per year. Dietary protein intake was estimated from a dietary history interview, as well as from urinary excretion of nitrogen (mean = 4.7 samples). Both methods showed a wide range of protein intake in all three groups of patients (0.6-2.3 g/kg body weight [BW]). The mean values did not differ between the groups, 1.30, 1.34, and 1.24 g/kg BW by interview, and 1.20, 1.10, and 1.13 g based on urinary nitrogen levels. There was no correlation between rate of decline of GFR and protein intake, even in those patients with no or minimal decline. These results do not support the hypothesis that dietary protein is a factor of importance in the development or progression of human diabetic nephropathy. 0 (Dietary Proteins); 0 (Hemoglobin A, Glycosylated); 62571-86-2 (Captopril); Osterby R, Gundersen HJ, Nyberg G, Aurell M. Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli. Diabetes 1987; 36(5):612-9. Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients. Adolescence; Adult; Basement Membrane/pathology; Capillaries/pathology; Diabetes Mellitus, Insulin-Dependent/pathology; Diabetic Nephropathies/pathology; Female; Human; Kidney Glomerulus/blood supply/ pathology; Male; Microscopy, Electron; Wysocki M, Persson B, Aurell M, Braide M, Bagge U, Andersson OK. Haemodynamic and haemorheological effects of hypervolaemic haemodilution in men with primary hypertension. J Hypertens 1987; 5(2):185-9. The haemorheological disturbances observed in primary hypertension arise mainly from haemoconcentration, which leads to an elevation of blood and plasma viscosity and increased aggregation of red blood cells (RBCs). We evaluated the rheological properties of blood and central haemodynamic indices in 13 men with untreated primary hypertension (WHO stage I and II), during a baseline period and after intravenous infusion of 1000 ml of 0.9% NaCl (within 12-15 min). The rheological properties studied were: whole blood viscosity (WBV), plasma viscosity (PV), haematocrit (HCT) and plasma fibrinogen concentration (PF). The central haemodynamic indices were: mean intra-arterial blood pressure (MAP), central venous pressure (CVP), cardiac index (CI), stroke volume index (SVI), total peripheral resistance index (TPRI) and the vascular hindrance index (VHI). Plasma renin activity (PRA) and plasma noradrenaline concentration (P-NA) were also measured. Volume expansion with saline caused haemodilution as expressed by a fall in HCT (P less than 0.001), WBV (P less than 0.001) and PV (P less than 0.01). At the same time, CVP, MAP and VHI increased (P less than 0.05) while PRA decreased (P less than 0.05) and P-NA remained unchanged. Mean values of the cardiac index (CI) and stroke volume index (SVI) did not change significantly. We did not observe any significant relationship between haemodynamic and haemorheological parameters, during baseline or between their respective changes after the infusion. The results indicate that although hypervolaemic haemodilution produced by saline infusion in hypertensive patients may improve blood flow properties (HCT, WBV, PV), blood pressure (BP) is not reduced; rather the converse is true. The reduction in HCT and hence the improved blood rheology, did not affect calculated vascular resistance. Thus, correction of WBV does not acutely normalize BP in primary hypertension. 51-41-2 (Norepinephrine); EC 3.4.23.15 (Renin); Andersson OK, Fagerberg B, Persson B, Aurell M, Hedner T. Hemodynamic and humoral adaptation to weight stable chronic sodium restriction in comparison with weight reduction in moderately obese hypertensive men. Acta Med Scand Suppl 1986; 714:65-9. 51-41-2 (Norepinephrine); EC 3.4.23.15 (Renin); Andersson OK, Persson B, Granerus G, Wysocki M, Aurell M, Hedner T et al. Release of atrial natriuretic peptide (alpha-hANP) and circulating noradrenaline in relation to central and renal hemodynamics and sodium output during acute volume load in hypertensive and normotensive men. Acta Med Scand Suppl 1986; 714:133-7. 51-41-2 (Norepinephrine); 85637-73-6 (Atrial Natriuretic Factor); EC 3.4.23.15 (Renin); Andersson OK, Persson B, Hedner T, Aurell M, Berglund G, Fagerberg B. Central haemodynamics, baroreceptor sensitivity and alpha 1-adrenoceptor-mediated vascular reactivity during weight-stable sodium restriction in obese men with hypertension. J Hypertens 1986; 4(1):101-7. Ten obese men (20-40% overweight) with previously untreated arterial hypertension (WHO stages I and II) were examined before and during sodium-restricted isocaloric diets. The mean (+/- s.d.) daily sodium excretion was reduced from 199 +/- 65 to +/- 25 mmol/24 h. Intra-arterial blood pressure (BP), cardiac output (CO), plasma volume, circulating and urinary noradrenaline (NA), plasma renin activity (PRA) and urinary aldosterone were measured. Vascular reactivity was assessed with intravenous bolus injections of 50, 100 and 200 micrograms phenylephrine, and baroreflex sensitivity was assessed with the R-R interval response to pressure elevations on electrocardiogram. Significant reductions in systolic BP from 163 +/- 18 to 147 +/- 17 mmHg and in diastolic BP from 97 +/- 7 to 88 +/- 9 mmHg occurred during salt restriction. Blood pressure reductions were correlated with changes of urinary sodium excretion (r = 0.71; P less than 0.05). No significant changes in CO, heart rate (HR) or stroke volume (SV) were observed; therefore, BP reduction was secondary to the fall in total peripheral resistance (TPR) from 21.8 +/- 4.1 to 19.0 +/- 4.1 units (P = 0.05). Plasma volume, as well as total blood volume, was not affected by the moderate sodium restriction, but PRA rose from 0.71 +/- 0.1 to 0.87 +/- 0.1 micrograms angiotensin 1/ml per h (P less than 0.05). Urinary aldosterone was increased from 32 +/- 12 to 54 +/- 9 nmol/24 h. No change in venous or arterial concentrations of NA or of urinary NA was observed.(ABSTRACT TRUNCATED AT 250 WORDS) 0 (Receptors, Adrenergic, alpha); 51-41-2 (Norepinephrine); 7440-23-5 (Sodium); Aurell M. Renin-angiotensinsystemets upptackare fostrade generationer i kreativt tankande. Lakartidningen 1986; 83(51):4364-5. English title: "The discoverer of the renin-angiotensin system trained generations in creative thinking (Robert Tigerstedt)" Germany; History of Medicine, 19th Cent.; History of Medicine, 20th Cent.; Human; Physiology/history; Portraits; Renin-Angiotensin System; Sweden; Aurell M, Granerus G. Oversikt for allmanlakare: njurfunktionsprov i vardagssjukvarden. Lakartidningen 1986; 83(8):604-7. English title: "An overview for general practitioners: kidney function tests in the everyday medical care" Adolescence; Adult; Aged; Child; Family Practice; Glomerular Filtration Rate; Human; Kidney Function Tests; Middle Age; Bjorck S, Nyberg G, Mulec H, Granerus G, Herlitz H, Aurell M. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. Br Med J (Clin Res Ed) 1986; 293(6545):471-4. The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/1.73 m2 body surface area (p less than 0.05) and the filtration fraction had decreased from 14.3 to 12.8% (p less than 0.025). During two years' treatment with captopril in 14 patients the mean arterial blood pressure had fallen by 5 mm Hg (p less than 0.005) and the deterioration in glomerular filtration rate had decreased from 10.3 to 2.4 ml/min/year (p less than 0.005). There was no correlation between the fall in blood pressure and the reduction in the deterioration of glomerular filtration rate. These findings suggest that the effects of angiotensin converting enzyme inhibition on renal haemodynamics protect renal function. Inhibitors of angiotensin converting enzyme should be considered for lowering blood pressure in patients with diabetic nephropathy. 62571-86-2 (Captopril); EC 3.4.15.1 (Peptidyl-Dipeptidase A); Bratt CG, Aurell M, Jonsson O, Nilsson S. Influence of intrapelvic pressure on excretion of sodium from human hydronephrotic kidneys. Eur Urol 1986; 12(5):334-9. The influence on urinary excretion of sodium (NNa . V) of intrapelvic pressure, urinary flow, and mean arterial blood pressure during forced diuresis was evaluated in 12 patients with unilateral hydronephrosis. Total and divided renal functions were measured using 51Cr-EDTA clearance and isotope renography. The amount of sodium, excreted by the obstructed kidney, decreased with higher maximum intrapelvic pressure and increased with higher differences between the mean arterial blood pressure and maximum intrapelvic pressure. The higher the concentrating ability, the lower the amount of sodium excreted by the obstructed kidney. There was a highly significant negative correlation between maximum intrapelvic pressure and urinary flow, but no correlation between mean arterial blood pressure and maximum intrapelvic pressure. Thus, obstructed kidneys with normal concentrating ability have the same excretion of sodium as the nonobstructed contralateral kidney during forced diuresis. Obstructed kidneys with decreased concentrating ability on the other hand excrete comparatively more sodium. This is probably due to a defect in sodium resorption. Adult; Aged; Blood Pressure; Diuresis; Female; Human; Hydronephrosis/physiopathology; Kidney Pelvis; Male; Middle Age; Natriuresis; Pressure; Urodynamics; Cedgard S, Herlitz H, Geterud K, Attman PO, Aurell M. Acute renal insufficiency after administration of low-osmolar contrast media. Lancet 1986; 2(8518):1281. 0 (Contrast Media); Delin K, Aurell M. Sodium and water depletion in ileostomy patients. Lancet 1986; 2(8512):924. 7440-23-5 (Sodium); Delin K, Aurell M. Hydration affects the result of a desmopressin test in adults. Scand J Urol Nephrol 1986; 20(2):143-4. Desmopressin tests to measure renal concentrating capacity, preceded by two different fluid regimens, have been compared in 19 adult subjects. The results show that peak osmolality in urine after 40 micrograms desmopressin intranasally is higher after fluid restriction. This observation confirms the need of a standardised fluid restriction before the desmopressin test. 16679-58-6 (Desmopressin); Herlitz H, Delin K, Hedner T, Granerus G, Aurell M. Dissociation of renin and noradrenaline release in the renal circulation. Studies on patients with renal hypertension. Scand J Urol Nephrol 1986; 20(3):213-6. Plasma renin activity (PRA) and noradrenaline concentration (NA) were measured in the renal veins (V) and arterial blood (A) in 30 patients investigated for renin-mediated hypertension. Both PRA and NA concentrations in arterial blood were above our reference limits and they were positively correlated. In 18 of the patients renin secretion was unilateral from the diseased side. Their renal vein NA concentration was always higher on that side, compared to the contralateral one, but there were V-A gradients for NA on both sides in all but two cases. In 15 of the patients with such lateralisation of renin secretion the changes of PRA and NA V-A gradients were determined 30-60 min after an i.v. injection of dihydralazine. Both PRA and NA increased more markedly in the renal vein on the affected side where the estimated renal plasma flow was lower than on the contralateral side. The NA gradients increased less than the PRA gradients when changes on the renin secreting side were compared in patients with proven increase of renin secretion. We conclude that patients with renal hypertension have a high sympathetic nervous activity as evidenced by increased plasma NA concentrations and (V-A) gradients for NA on both sides. The release of NA into the renal circulation in renin mediated hypertension is thus not invariably accompanied by renin release. The higher renal vein NA concentration on the involved renin secreting side is explained by reduced RPF on this side. 484-23-1 (Dihydralazine); 51-41-2 (Norepinephrine); 86-54-4 (Hydralazine); EC 3.4.23.15 (Renin); Mathillas O, Attman PO, Aurell M, Delin K, Granerus G. Conflicting results between glomerular filtration rate and serum creatinine measurements in chronic renal failure. Contrib Nephrol 1986; 53:71-3. 0 (Dietary Proteins); 60-27-5 (Creatinine); Aurell M, Rudin A. Effect of captopril in Bartter's syndrome. Nephron 1985; 39(1):68. 147-85-3 (Proline); 62571-86-2 (Captopril); 7440-09-7 (Potassium); Delin K, Granerus G, Aurell M. Renal vein renin studies in renovascular hypertension--do they really help? J Hypertens 1985; 3(6):659-60. EC 3.4.23.15 (Renin); Fagerberg B, Andersson OK, Lindstedt G, Waldenstrom J, Aurell M. The sodium intake modifies the renin-aldosterone and blood pressure changes associated with moderately low energy diets. Acta Med Scand 1985; 218(2):157-64. Thirty middle-aged, moderately obese men with untreated mild hypertension were allocated to two groups of 15 men each. Both groups were placed on energy-reduced diets (5.1 MJ/day) for 9-11 weeks which resulted in similar losses of body mass (8.5 kg). In group I the low energy diet was supplemented with sodium chloride leading to no change in urinary sodium excretion. During dieting there were significant reductions of plasma renin activity (PRA) and urinary excretion of noradrenaline and aldosterone. Heart rate but not mean arterial pressure (MAP) decreased significantly. Then followed a period of sodium restriction which resulted in a significant decrease in MAP and an increase in aldosterone excretion. In group II there was a reduction of sodium intake by about 80 mmol as judged from determinations of urinary sodium excretion. In this group the energy restriction was not accompanied by any changes in PRA or urinary excretion of aldosterone, whereas urinary noradrenaline excretion, heart rate and MAP decreased significantly. Urinary adrenaline excretion remained unchanged. It is concluded that the hypotensive response to moderate energy and sodium reduction cannot be explained by changes in the renin-aldosterone. system. 51-41-2 (Norepinephrine); 52-39-1 (Aldosterone); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Feddersen K, Aurell M, Delin K, Haggendal J, Aren C, Radegran K. Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin. Acta Anaesthesiol Scand 1985; 29(2):224-30. Infusion of prostacyclin during cardiopulmonary bypass (CPB) reduces platelet activation, diminishes postoperative blood loss and decreases arterial blood pressure. In spite of continuous prostacyclin infusion, there is a delayed gradual rise in arterial pressure and resistance from low initial levels. We measured epinephrine (E), norepinephrine (NE), serotonin (5-HT), angiotensin II (ATII) and arginine-vasopressin (AVP) in plasma and carried out hemodynamic studies in 19 patients operated for coronary vascular disease. Eight patients served as a control group and were subjected to routine CPB. Eleven patients received prostacyclin 50 ng/kg/min during CPB. E and NE increased four- to sixfold during CPB from about 0.5 ng/ml (P less than 0.001). There was no difference between the groups. During CPB AVP increased sixfold from about 20 pg/ml in both groups (P less than 0.001), decreased early after CPB and increased again to high levels 3 h after CPB. The combined action of E, NE and AVP is of likely importance for the rise in systemic vascular resistance and/or need of vasodilation during CPB in the control group. ATII did not increase in the control group, but increased fourfold to about 20 pg/ml (P less than 0.01) during CPB in the prostacyclin group. The addition of AT II to E, NE and AVP seems responsible for the gradual return of arterial pressure and resistance during prostacyclin infusion. Postoperative hypertension and/or need of vasodilation 3 h after CPB was associated with high AVP levels in both groups. Hypotension caused by prostacyclin infusion did not increase E, NE or AVP above levels produced by CPB and moderate hypotension alone. 0 (Catecholamines); 11128-99-7 (Angiotensin II); 113-79-1 (Argipressin); 35121-78-9 (Epoprostenol); 50-67-9 (Serotonin); 51-41-2 (Norepinephrine); 51-43-4 (Epinephrine); Herlitz H, Aurell M, Bjorck S, Granerus G. Renal effects of felodipine in hypertensive patients with reduced renal function. Drugs 1985; 29 Suppl 2:192-7. The new calcium antagonist felodipine with a pronounced arteriolar dilating capacity was used to treat 11 patients with severe hypertension resistant to treatment (4 with essential hypertension, 5 with renoparechymatous hypertension, 2 with renovascular hypertension). Mean glomerular filtration rate for 10 patients was 34 +/- 27 ml/min/1.73 m2 body surface area (51Cr-EDTA clearance) before felodipine. One patient was on haemodialysis treatment. Mean arterial blood pressure in the outpatient clinic was 206 +/- 39/119 +/- 18 mm Hg in spite of treatment with 3 or more antihypertensive drugs. All but 2 patients had been given an angiotensin converting-enzyme inhibitor without success. All vasodilating agents were discontinued and the following morning 5 to 10 mg felodipine was given orally. This resulted in a reduction of average supine blood pressure from 190/110 mm Hg to 150/90 mm Hg during the first hour. The antihypertensive effect was unchanged during 6 hours and the drug was subsequently administered twice or three times a day. Mean systolic and diastolic blood pressure after 1 month was 155 +/- 19/91 +/- 12 mm Hg. Eight patients showed a favourable long term response with a mean systolic and diastolic blood pressure of 154 +/- 17/89 +/- 6mm Hg after 6 months. One patient died from his underlying disease after 2 months and 1 patient discontinued treatment because of ankle oedema after 6 weeks. In the long term treated patients with glomerular filtration rates greater than 15 ml/min/1.73m2 all but 1 showed an improved renal function by 26 +/- 19% (n = 5) after initiation of felodipine therapy. In 2 cases with very low glomerular filtration rate (6 to 7 ml/min/1.73m2) the deterioration of renal function continued after felodipine, but at a slower rate. It is concluded that felodipine decreased blood pressure dramatically in patients with severe hypertension where a majority of the cases had been resistant to a previous therapy. The drug appeared safe also in advanced renal insufficiency. 0 (Antihypertensive Agents); 21829-25-4 (Nifedipine); 72509-76-3 (Felodipine); Herlitz H, Sultan B, Jonsson O, Karlsson K, Ljungblad U, Aurell M. Cellular sodium transport in pregnancy induced hypertension. Acta Med Scand Suppl 1985; 693:15-8. 7440-23-5 (Sodium); Ljungman S, Aurell M, Hartford M, Wikstrand J, Berglund G. Renal function and renal haemodynamics before and after 7 years' antihypertensive treatment in men with primary hypertension. Acta Med Scand Suppl 1985; 693:89-92. 0 (Antihypertensive Agents); Mathillas O, Attman PO, Aurell M, Blohme I, Brynger H, Granerus G et al. Long-term outcome of renal function and proteinuria in kidney transplant donors. Proc Eur Dial Transplant Assoc Eur Ren Assoc 1985; 21:574-9. Ten to eighteen years after donor uninephrectomy (UN) there was no evidence for deterioration of renal function. The mean urinary albumin excretion was slightly increased. There was a positive correlation between the assessed protein intake at investigation and the glomerular filtration rate (GFR). Adult; Aged; Comparative Study; Female; Glomerular Filtration Rate; Human; Kidney/physiopathology/transplantation; Kidney Transplantation; Male; Middle Age; Proteinuria/physiopathology; Time Factors; Mathillas O, Attman PO, Aurell M, Blohme I, Brynger H, Granerus G et al. Proteinuria and renal function in kidney transplant donors 10-18 years after donor uninephrectomy. Ups J Med Sci 1985; 90(1):37-42. Ten to eighteen years after donor uninephrectomy (UN) the compensatory increase in renal function is maintained. Albuminuria was slightly increased in a few donors compared to the controls. We found no evidence for donor uninephrectomy to carry a risk for progressive renal failure. Further studies 2-3 decades after UN will provide additional insight in how UN affects the development of proteinuria and renal function. Adult; Aged; Albuminuria/etiology; Female; Glomerular Filtration Rate; Human; Kidney/physiology/transplantation; Kidney Transplantation; Male; Middle Age; Nephrectomy/adverse effects; Proteinuria/etiology; Time Factors; Tissue Donors; Atlas SA, Hesson TE, Sealey JE, Dharmgrongartama B, Laragh JH, Ruddy MC et al. Characterization of inactive renin ("prorenin") from renin-secreting tumors of nonrenal origin. Similarity to inactive renin from kidney and normal plasma. J Clin Invest 1984; 73(2):437-47. Inactive renin comprises well over half the total renin in normal human plasma. There is a direct relationship between active and inactive renin levels in normal and hypertensive populations, but the proportion of inactive renin varies inversely with the active renin level; as much as 98% of plasma renin is inactive in patients with low renin, whereas the proportion is consistently lower (usually 20-60%) in high-renin states. Two hypertensive patients with proven renin-secreting carcinomas of non-renal origin (pancreas and ovary) had high plasma active renin (119 and 138 ng/h per ml) and the highest inactive renin levels we have ever observed (5,200 and 14,300 ng/h per ml; normal range 3-50). The proportion of inactive renin (98-99%) far exceeded that found in other patients with high active renin levels. A third hypertensive patient with a probable renin-secreting ovarian carcinoma exhibited a similar pattern. Inactive renins isolated from plasma and tumors of these patients were biochemically similar to semipurified inactive renins from normal plasma or cadaver kidney. All were bound by Cibacron Blue-agarose, were not retained by pepstatin-Sepharose, and had greater apparent molecular weights (Mr) than the corresponding active forms. Plasma and tumor inactive renins from the three patients were similar in size (Mr 52,000-54,000), whereas normal plasma inactive renin had a slightly larger Mr than that from kidney (56,000 vs. 50,000). Inactive renin from each source was activated irreversibly by trypsin and reversibly by dialysis to pH 3.3 at 4 degrees C; the reversal process followed the kinetics of a first-order reaction in each instance. The trypsin-activated inactive renins were all identical to semipurified active renal renin in terms of pH optimum (pH 5.5-6.0) and kinetics with homologous angiotensinogen (Michaelis constants, 0.8-1.3 microM) and inhibition by pepstatin or by serial dilutions of renin-specific antibody. These results indicate that a markedly elevated plasma inactive renin level distinguishes patients with ectopic renin production from other high-renin hypertensive states. The co-production of inactive and active renin by extrarenal neoplasms provides strong presumptive evidence that inactive renin is a biosynthetic precursor of active renin. The unusually high proportion of inactive renin in plasma and tumor extracts from such patients is consistent with ineffective precursor processing by neoplastic tissue, suggesting that if activation of "prorenin" is involved in the normal regulation of active renin levels it more likely occurs in the tissue of origin (e.g., kidney) than in the circulation. 0 (Enzyme Precursors); EC 3.4.23.15 (Renin); EC 3.4.99.- (prorenin); Aurell M. Physiological aspects of the renin-angiotensin system and peroral angiotensin converting enzyme inhibition. Scand J Urol Nephrol Suppl 1984; 79:9-12. 11128-99-7 (Angiotensin II); EC 3.4.15.1 (Peptidyl-Dipeptidase A); EC 3.4.23.15 (Renin); Bjorck S, Delin K, Herlitz H, Larsson O, Aurell M. Renin secretion in advanced diabetic nephropathy. Scand J Urol Nephrol Suppl 1984; 79:53-7. Low basal and stimulated plasma renin activity (PRA) levels have been reported in patients with diabetic nephropathy (DN). We have measured PRA before and after stimulation with captopril in 28 patients with DN and in 25 control patients. Renal function impairment was similar in both groups. Most patients were treated with furosemide. In 19 patients with DN the PRA-response to dihydralazine was also studied. PRA before and after captopril were higher in the DN than in the control group (p less than 0.001). PRA increased from 4.6 +/- 3.6 to 6.3 +/- 5.3 in the DN, and from 1.8 +/- 2.7 to 2.7 +/- 3.4 in the control patients. The increases in PRA, caused by decreased angiotensin II feed-back inhibition, were comparable. PRA did not increase after dihydralazine despite a pronounced blood-pressure reduction. The difference in response to these stimuli indicate selective lesions involving both the sympathetic innervation and the renal baroreceptor function in DN. Overhydration is a plausible explanation to the low PRA earlier reported in DN. The results thus indicate that a preserved renin secretion capacity is present in DN. Differences in PRA between the both groups can only partly be explained by other factors than DN. Our findings indicate a role for the reninangiotensin-system in hypertension in DN. 0 (Chlorides); 11128-99-7 (Angiotensin II); 484-23-1 (Dihydralazine); 62571-86-2 (Captopril); EC 3.4.23.15 (Renin); Bjorck S, Johansson SL, Aurell M. Acute renal failure caused by a rapidly progressive arterio-occlusive syndrome--Kohlmeier-Degos' disease? Scand J Urol Nephrol 1984; 18(4):343-6. A 45-year-old man who presented with acute renal insufficiency is described. He deteriorated during haemodialysis, developed severe gastrointestinal bleedings, and died two months after his initial admission. Histopathological changes responsible for his renal disease were focal narrowing and occlusion of the arteries of the kidneys due to concentric intimal proliferation. These findings are consistent with those described in Kohlmeier-Degos' disease, a fatal cutaneo-intestinal arterio-occlusive syndrome. Therefore we consider our patient to represent a case of this disease, which may be added to the list of rare causes of acute renal failure. Arterial Occlusive Diseases/complications/pathology; Arteritis/complications/ pathology; Case Report; Human; Kidney/blood supply; Kidney Failure, Acute/etiology; Male; Middle Age; Syndrome; Delin K, Aurell M, Granerus G. Preoperative diagnosis of renovascular hypertension. The use of acute stimulation of renin secretion. Acta Med Scand 1984; 215(4):363-9. The gain in the diagnostic power of the routine preoperative bilateral renal vein renin investigation by the inclusion of an acute stimulation of renin release was studied in 25 hypertensive patients with fibromuscular (FMD) and 44 with arteriosclerotic (AS) renovascular disease. Nine FMD and 17 AS patients had renal vein renin ratios greater than or equal to 1.50 under unstimulated conditions. Of these 26 patients, 8 in each group improved after surgical treatment. Among the 14 FMD and 24 AS patients with ratios less than 1.50, another 9 FMD and 7 AS patients improved after operation. After acute stimulation of renin release, no less than 18 FMD and 26 AS patients had a unilateral renin secretion from the diseased kidney and of these, 14 FMD and 14 AS patients were successfully treated with operation of the stenosis. Thus the stimulation was necessary for correct preoperative diagnosis in 38% of 32 successfully operated patients, and at the same time the predictive value of a negative test increased from 0.58 to 0.80. It is concluded that acute stimulation of renin release greatly improves the diagnostic power of the renal vein renin investigation in renovascular hypertension. 54-31-9 (Furosemide); EC 3.4.23.15 (Renin); Delin K, Aurell M, Herlitz H. Saluretics and converting-enzyme blockade in the treatment of resistant hypertension. Acta Pharmacol Toxicol (Copenh) 1984; 54 Suppl 1:53-6. Blockade of the actions of the renin-angiotensin-aldosterone axis by inhibition of the angiotensin-converting enzyme with captopril is a new tool in the field of hypertension. As treatment with captopril makes pressure control volume-dependent, the addition of a saluretic is considered the best choice if an additional hypotensive agent is needed. The reason for and experience of the use of captopril in combination with saluretics for treatment of severe hypertension is reviewed. Published results indicate that captopril alone is insufficient, but as many as a third of the patients with previously uncontrollable hypertension manage well when a saluretic is added. Only one in six remains uncontrolled despite the addition of several other hypotensive agents. These observations apply to both essential and secondary forms of hypertension. 0 (Diuretics); 0 (Electrolytes); 62571-86-2 (Captopril); EC 3.4.15.1 (Peptidyl-Dipeptidase A); Delin K, Aurell M, Herlitz H. Captopril in the treatment of hypertension in predialytic end-stage renal disease. Contrib Nephrol 1984; 41:299-303. 0 (Antihypertensive Agents); 147-85-3 (Proline); 60-00-4 (Edetic Acid); 60-27-5 (Creatinine); 62571-86-2 (Captopril); EC 3.4.23.15 (Renin); Delin K, Fasth S, Andersson H, Aurell M, Hulten L, Jagenburg R. Factors regulating sodium balance in proctocolectomized patients with various ileal resections. Scand J Gastroenterol 1984; 19(2):145-9. Patients subjected to proctocolectomy together with an ileal resection will lose increased amounts of sodium with the ileostomy excreta and may develop sodium and water depletion. Studies of sodium balance and measurements of renin activity, aldosterone, and arginine vasopressin in plasma were made in 23 such patients, 8 of them under metabolic-ward conditions while receiving various salt loads. Salt loss never resulted in subnormal sodium levels in serum. The earliest sign of salt depletion was a nearly total inhibition of renal sodium excretion, which could precede activation of the renin-aldosterone axis in these patients. Secretion of vasopressin remained unaffected by sodium-water depletion and by activation of the renin system. The routine monitoring of these patients should include measurements of renal sodium excretion. Measurement of renin and aldosterone levels should be used for evaluation of the severity of a sodium deficiency. 113-79-1 (Argipressin); 52-39-1 (Aldosterone); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Folkow B, Aurell M, Friberg P, Gothberg G, Hallback-Nordlander M, Karlstrom G et al. Cardiovascular studies in rats with respect to some functional and structural relationships of relevance in hypertension and ordinary aging. Clin Exp Hypertens A 1984; 6(1-2):587-98. Five current lines of cardiovascular studies in rats are outlined, mainly dealing with some functional and structural relationships of particular relevance for hypertension and ordinary aging: 1. Characteristics of the smooth muscles and their neurogenic control in 'Windkessel' arteries, conduit arteries, precapillary resistance vessels and venous capacitance vessels from normotensive rats (WKY) with comparisons to rats with primary hypertension (SHR). 2. Different types of structural renovascular adaptation, comparing aging with advancing SHR hypertension, with 'high-pressure' and 'low-pressure' kidneys in one-clip, two-kidney renal hypertension, and with hypertrophied kidneys in uni-nephrectomized normotensive rats. 3. Relationships between 'structural autoregulation', wall distensibility, vascular reactivity and smooth muscle sensitivity in SHR and WKY hindquarter resistance vessels along with aging. 4. Relationships between wall thickness, luminal dimension and contractility in left ventricles from SHR and WKY during aging, and when one-clip, two-kidney hypertension is superimposed. 5. Interference with the capacity of the neurohormonal mechanisms counteracting blood loss in rats when on chronic low-salt diet. Aging; Animal; Cardiomegaly/physiopathology; Cardiovascular System/physiopathology; Electric Stimulation; Hypertension/pathology/ physiopathology; Muscle, Smooth, Vascular/pathology; Rats; Rats, Inbred Strains; Sympathetic Nervous System/physiopathology; Vascular Resistance; Vasoconstriction; Gudmundsson O, Andersson OK, Aurell M, Wikstrand JM, Berglund GL. Calf muscle haemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with a familial predisposition to hypertension: changes during increased salt intake. J Hypertens 1984; 2(3):291-6. Blood pressure, plethysmographically determined muscle blood flow in the calf at rest and during maximal dilatation, plasma renin activity, angiotensin II and plasma and urinary aldosterone were determined in normotensive men with a positive family history of hypertension (n = 17) and in an age- and weight-matched control group (n = 15) during usual sodium intake and after four weeks of increased salt intake. On normal salt intake resting muscle blood flow was significantly lower and resting resistance and resting vascular tone significantly higher in those with a positive family history, reflecting a stronger smooth muscle contraction of the resistance vessels in the calf at rest. Flow and resistance at maximal dilatation did not differ between the groups, indicating no difference in the structural design of the resistance vessels in the calf. Plasma angiotensin II and urinary aldosterone were not significantly different between the two groups. Plasma renin activity was, however, significantly higher in those with a positive family history which might be interpreted as increased renal sympathetic activity in the genetically predisposed subjects. After four weeks of increased salt intake no significant changes were noted in blood pressure, muscle blood flow and resistance at rest or at maximal dilatation in either of the two groups. Plasma renin activity and angiotensin II decreased significantly in both groups after 10 days of increased salt but tended to return to normal values at the end of the fourth week. Plasma aldosterone and urinary aldosterone excretion were equally and significantly decreased in both groups giving no evidence for an inadequate suppression of aldosterone in subjects genetically predisposed to hypertension. 11128-99-7 (Angiotensin II); 52-39-1 (Aldosterone); 7647-14-5 (Sodium Chloride); EC 3.4.23.15 (Renin); Herlitz H, Ahlmen J, Aurell M, Blohme I, Brynger H, Delin K et al. Captopril in hypertension after renal transplantation. Scand J Urol Nephrol Suppl 1984; 79:111-4. The experience with captopril is limited in patients who are hypertensive after renal transplantation. An increased risk of side effects has been expected because of immunosuppressive therapy and a reduced renal function. We have used captopril in 58 transplanted patients with hypertension. On previous antihypertensive treatment diastolic blood pressure could not be maintained below 100 mm Hg. All patients were on immunosuppressive therapy using prednisolone in combination with azathioprine or cyclosporin. Before captopril treatment the mean s-creatinine concentration was 225 +/- 143 mumol/l. Fifty-four patients were treated for more than four weeks and 28 of them for six months or more. The mean daily dose of captopril was 90 mg. All patients also used furosemide and 2/3 were on a beta-blocker. Captopril was discontinued in nine cases within the first two months, in three because of an unsatisfactory effect on BP, in four because of side effects and in two after successful treatment of a renal artery stenosis of the transplant. The patients who were treated with captopril within the first year after transplantation responded better than patients where treatment was started more than one year after transplantation (p less than 0.05). Half of the patients given captopril early even showed a decrease of s-creatinine during treatment. Captopril in combination with a diuretic and a beta-blocker reduces blood pressure in patients with treatment resistant hypertension following renal transplantation. The risk for serious side effects is small provided that the captopril dose is low and white cell counts and s-creatinine levels are closely monitored. 11128-99-7 (Angiotensin II); 147-85-3 (Proline); 62571-86-2 (Captopril); EC 3.4.23.15 (Renin); Herlitz H, Edeno C, Mulec H, Westberg G, Aurell M. Captopril treatment of hypertension and renal failure in systemic lupus erythematosus. Nephron 1984; 38(4):253-6. Captopril, an angiotensin-converting enzyme inhibitor, was used to treat 14 patients with lupus nephritis and severe hypertension. All patients had reduced renal function and were on regular immunosuppressive therapy with corticosteroids and azathioprine. The initial dosage of captopril was reduced according to the level of renal impairment. 11 patients were treated for more than 6 months. Excellent blood pressure control was achieved with captopril, from a mean of 178 +/- 7/110 +/- 4 to 145 +/- 5/92 +/- 3 mm Hg at 6 months, usually in combination with a diuretic only. In 5 cases, a beta-blocker was added. In 3 patients, captopril therapy was discontinued within the 1st month of treatment. 1 patient did not respond to captopril at all; 1 patient had a rejection crisis and required dialysis; in 1 case, a general exanthema developed within 3 weeks and captopril medication was stopped. In addition to blood pressure control, renal function improved in 7 of the long-term-treated patients (mean increase in glomerular filtration rate 73 +/- 34%). In 3 patients, a continued slow deterioration renal function occurred, and in 1 patient, renal function remained unchanged. It is concluded that captopril is an effective antihypertensive drug in patients with systemic lupus erythematosus (SLE). Captopril treatment increased renal function in 64% of patients on long-term therapy. Not only optimal blood pressure control but other factors may also contribute to this beneficial effect, such as drug-induced prostaglandin release potentiating immunosuppressive treatment. Captopril may in fact be the drug of choice for the treatment of SLE patients with severe hypertension. 0 (Antihypertensive Agents); 0 (Immunosuppressive Agents); 147-85-3 (Proline); 62571-86-2 (Captopril); Larsson O, Attman PO, Aurell M, Frisk B, Brynger H. Survival in end-stage diabetic renal disease. A prospective study of 100 kidney transplant patients. Acta Med Scand 1984; 216(4):393-402. The results of renal transplantation in patients with diabetes mellitus were studied in 100 consecutive patients transplanted between Dec. 1972 and June 1982. The study period was divided into two parts, 1972-76 (era I, 21 patients, 18 with juvenile onset diabetes) and 1977-82 (era II, 79 patients, 72 with juvenile onset diabetes). A group of 168 non-diabetic patients, aged 20-54 years, receiving primary grafts during the same period served as controls to the 72 juvenile onset diabetics from era II. The three-year actuarial patient survival of transplanted diabetics improved from 48% during era I to 76% during era II and was then not significantly inferior to that of the non-diabetic controls. The three-year actuarial graft survival rate was significantly higher for recipients of kidneys from living related donors than for those who had received kidneys from cadaveric donors (CD) among both diabetic and non-diabetic patients. However, the three-year graft survival rate was significantly higher (56%) for non-diabetic than diabetic CD recipients (37%). The overall survival in diabetes mellitus was strongly influenced by the outcome of retransplantation during era II (12 patients). Thus, 69 patients were alive, 64 with a functioning graft, at the end of the observation period. 0 (Immunosuppressive Agents); Nyberg G, Larsson O, Westberg NG, Aurell M, Jagenburg R, Blohme G. A platelet aggregation inhibitor--ticlopidine--in diabetic nephropathy: a randomized double blind study. Clin Nephrol 1984; 21(3):184-7. A randomized double blind trial was performed to investigate the effect of the platelet aggregation inhibitor ticlopidine on the rate of decline in renal function in diabetic nephropathy. Twenty-two patients with insulin dependent diabetes complicated by nephropathy completed the trial--11 on ticlopidine, and 11 on placebo for one year. Ticlopidine effectively reduced platelet aggregation in vitro. Renal clearance of 51Cr-EDTA declined from 39 +/- 10 to 30 +/- 13 ml/min per 1.73 m2 body surface in the ticlopidine group and from 42 +/- 9 to 39 +/- 13 in the placebo group. The difference in decline between the two groups was not significant. In the ticlopidine group renal function expressed as the slope coefficient for 1/S-creatinine per month remained the same as before the trial. It is concluded that although there is much evidence to suggest a role of platelets in the development or progression of diabetic nephropathy treatment with ticlopidine could not prevent this process. 0 (Thiophenes); 55142-85-3 (Ticlopidine); 60-27-5 (Creatinine); Ohman P, Aurell M, Asplund J, Conradsson T, Delin K, Forslund T et al. A long-term follow-up of patients with essential hypertension treated with captopril. Acta Med Scand 1984; 216(1):53-6. Seventy-four patients from four short-term studies of captopril in mild-moderate essential hypertension continued in a cooperative long-term efficacy and tolerance program. The duration of observation is 2- greater than 4 years, the total treatment time being 2434 months. No development of resistance to therapy was observed. The total daily dose of captopril has been gradually decreased and in 20 patients changed from t.i.d. to b.i.d. regime. The drug has been well tolerated and only few and mild side-effects have been observed after the initial titration period. The drop-outs (n = 19) were mostly due to non-medical causes (n = 14). Except for one case of proteinuria, no laboratory abnormalities were detected and there were no signs of long-term toxicity. 147-85-3 (Proline); 525-66-6 (Propranolol); 58-93-5 (Hydrochlorothiazide); 62571-86-2 (Captopril); Rudin A, Granerus G, Aurell M. Effects of prostaglandin synthetase inhibition on captopril-induced changes in renal function in Bartter's syndrome. Scand J Urol Nephrol Suppl 1984; 79:59-62. Three patients with Bartter's syndrome were studied under metabolic ward conditions. Renal function and the reninangiotensin system were evaluated in three different settings: before and during captopril treatment and during administration of captopril and indomethacin. Captopril induced renal vasodilation with an increase in renal plasma flow by 23%. The addition of indomethacin abolished this change. Captopril increased the release of renin and the concentration of angiotensin II in plasma decreased without being completely normalized. Indomethacin thereafter reduced plasma concentration of renin, which was, however, still higher than the control level. The plasma concentration of angiotensin II did not change significantly. In conclusion, prostaglandin synthetase inhibition annihilated the effect of captopril on renal hemodynamics and renin release. 147-85-3 (Proline); 53-86-1 (Indomethacin); 62571-86-2 (Captopril); EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthase); Rudin A, Sjogren B, Aurell M. Low urinary calcium excretion in Bartter's syndrome. N Engl J Med 1984; 310(18):1190. 7440-70-2 (Calcium); Sigstrom L, Aurell M, Jodal U. Angiotensin converting enzyme inhibitor treatment of hypertension in infancy and childhood. Scand J Urol Nephrol Suppl 1984; 79:107-9. Captopril treatment was given to 30 children aged 8 months to 16 years (mean age 10.1 years) with renal hypertension when combinations of one or more of betablockers, diuretics, clonidine and hydralazine had failed to reduce blood pressure in the majority of the children. Dosages of captopril varied between 0.5 and 11.0 mg/kg BW, which was combined with furosemide in 15 cases, betablockers in three cases, betablockers and clonidine in two cases. Pretreatment mean plasma renin activity (PRA) was 7.9 (0.8-89.4) ng AT/ml/h in 22 of the 30 children and 59% had more than 2.0 ng AT/ml/h. Blood pressure fell from a mean of 158/109 (range 135/75 - 240/140) mm Hg to a mean of 120/76 (range 110/65 - 150/100) mm Hg. Mean duration time was 10.1 months (1-47 months). Skin rash occurred in three cases and taste disturbance in one case. Falling glomerular filtration rate was observed in two children with diseases of the renal vessels. After withdrawal of captopril renal function returned to the pretreatment level. Angiotensin converting enzyme inhibition for treatment of hypertension in childhood has proved to be efficient and safe in these 30 children. 147-85-3 (Proline); 62571-86-2 (Captopril); EC 3.4.15.1 (Peptidyl-Dipeptidase A); EC 3.4.23.15 (Renin); Aurell M, Rudin A. Effect of captopril on blood pressure, renal function, the electrolyte balance and the renin-angiotensin system in Bartter's syndrome. Nephron 1983; 33(4):274-8. 3 patients with Bartter's syndrome were studied under metabolic ward conditions before and during administration of captopril 25 mg t.i.d. The drug induced an immediate and sustained reduction of blood pressure (by 14 and 18% after 1 h and 3 days, respectively) with no change in heart rate. During treatment renal plasma flow increased by 29%, but the glomerular filtration rate was unchanged. Renal vascular resistance decreased by 41%. There was an increase in urinary sodium excretion with a corresponding reduction of body weight. The potassium balance was not affected. The concentration of angiotensin II became normal but the plasma renin concentration rose tenfold. Plasma renin substrate, initially rather low, was further reduced. The blood pressure responsiveness to angiotensin II increased without being completely normalized. An abnormal production of vasodilating prostaglandins is thought to be an important feature of Bartter's syndrome. Our findings, notably the marked renal vasodilatation, may reflect the effect of these prostaglandins when unopposed by an increased angiotensin II production. 147-85-3 (Proline); 62571-86-2 (Captopril); 7440-09-7 (Potassium); 7440-23-5 (Sodium); Bendz H, Andersch S, Aurell M. Kidney function in an unselected lithium population. A cross-sectional study. Acta Psychiatr Scand 1983; 68(5):325-34. We studied kidney function in 124 short-term and long-term lithium outpatients from a population of 127 patients. Glomerular and distal tubular function were measured and correlated with a number of demographic and treatment variables. There was a significant negative correlation between age and glomerular filtration rate. There were no other significant correlations. Tubular function was below normal in 51% of the patients. Glomerular function was below normal in 3% of the patients. We conclude that lithium treatment in non-toxic dose affects kidney function and that tubular function is more affected than glomerular function. Tubular function probably is better than our figures indicate, glomerular function not as good. Types of lithium preparation do not affect kidney function differently nor does combined treatment with neuroleptics. 0 (Antipsychotic Agents); 7439-93-2 (Lithium); Bjorck S, Herlitz H, Nyberg G, Granerus G, Aurell M. Effect of captopril on renal hemodynamics in the treatment of resistant renal hypertension. Hypertension 1983; 5(5 PT 2):III152-3. The effects of 6 weeks of treatment with captopril on the renal hemodynamics of 16 patients with treatment-resistant renal hypertension (six had diabetic nephropathy, seven had other renal parenchymatous disease, and three had renovascular disease) were studied. Significant changes in glomerular filtration rate, filtration fraction, plasma renin activity, urinary aldosterone, and mean blood pressure were noted in the patients with renal parenchymatous disease, but not in those with diabetic nephropathy. Renal blood flow remained unchanged in all patients. Captopril was well tolerated. 147-85-3 (Proline); 62571-86-2 (Captopril); Bratt CG, Aurell M, Granerus G, Nilsson S. Late results of pyeloplasty for idiopathic hydronephrosis in adults. Scand J Urol Nephrol 1983; 17(3):329-35. A series of 91 cases of unilateral obstruction of the pelviureteric junction is reviewed. Primary nephrectomy was performed in 13 cases (14%) because of severe hydronephrosis and renal function less than 10% that of the normal kidney. Pyeloplasty was performed according to Anderson-Hynes in 74 cases and with a Culp-De Weerd flap in four cases. Nephrostomy was performed concomitantly with the pyeloplasty in 14 cases. The parenchymal function was normal before pyeloplasty in 78% of the 78 kidneys, though the drainage function was severely impaired in 76 of the kidneys and moderately impaired in two. Urine cultures were positive before pyeloplasty in two patients, and 13 of the treated kidneys contained calculi. Follow-up examination was performed 5 to 12 years (mean 8.5 years) after pyeloplasty in all 78 patients. Of the 17 kidneys with preoperatively impaired parenchymal function, 12 (71%) showed improvement. The drainage function was improved in 68 (91%) of the 75 studied kidneys. Persistently impaired drainage function after pyeloplasty was found only in kidneys with infection secondary to retrograde passage of a ureteral catheter for treatment of postoperative urinary leakage. Urinary infection occurred in 11 of the 33 cases with such leakage. Retrograde ureteral catheterization thus favoured the occurrence of urinary infection. Its importance as a risk factor for severe infection was shown by the necessity for secondary nephrectomy in three cases. Since nephrostomy tended to reduce the incidence of urinary leakage, and thereby the need for indwelling ureteral catheter, and since nephrostomy as such was not associated with urinary infection, we recommend its use in the management of idiopathic hydronephrosis. Adult; Aged; Female; Follow-Up Studies; Human; Hydronephrosis/surgery; Kidney Calculi/complications; Kidney Pelvis/surgery; Male; Middle Age; Nephrectomy; Postoperative Complications; Urinary Tract Infections/etiology; Delin K, Aurell M. Renal artery stenosis: to operate or not? Lancet 1983; 2(8364):1420. Decision Making; Human; Hypertension, Renovascular/diagnosis; Renal Artery Obstruction/surgery; Delin K, Aurell M, Granerus G. Renal vein renin on acute stimulation in diagnosis of renal hypertension. Acta Med Scand Suppl 1983; 677:85-8. 484-23-1 (Dihydralazine); EC 3.4.23.15 (Renin); Gothberg G, Lundin S, Aurell M, Folkow B. Response to slow, graded bleeding in salt-depleted rats. J Hypertens Suppl 1983; 1(2):24-6. The response to slow bleeding was studied in rats on low sodium intake (0.04%) versus 'ordinary' (0.4%) intake. After 12 days on the diets acute experiments were performed on paired, conscious rats. Initially the salt-depleted rats had slightly lower mean arterial pressure (121 +/- 2 versus 129 +/- 3 mmHg, n = 30 pairs, P less than 0.02). Heart rate (HR), cardiac output, plasma volume, extracellular volume and plasma renin activity (PRA) did not differ significantly, while haematocrit was slightly higher in the salt-depleted rats (46.5 +/- 0.3 versus 45.1 +/- 0.5%, P less than 0.05). The animals were then slowly bled 1 ml every 5 min until mean arterial pressure (MAP) fell and remained below 50 mmHg. The controls tolerated up to a 55 +/- 1% loss of initial blood volume, while the salt-depleted rats turned into irreversible shock already after losing 38 +/- 2% (P less than 0.001). At this stage compensatory haemodilution, HR and PRA increases were less pronounced than in the controls, suggesting that chronic sodium restriction had somehow interfered with the neurohormonal defences against accidental salt fluid losses. Animal; Blood Pressure; Cardiac Output; Diet, Sodium-Restricted; Heart Rate; Hematocrit; Hemorrhage/physiopathology; Male; Rats; Rats, Inbred Strains; Grenabo L, Aurell M, Delin K, Holmlund D, Sjodin JG. Antidiuretic hormone levels and the effect of indomethacin on ureteral colic. J Urol 1983; 129(5):941-3. We treated 25 patients with ureteral colic and urographically verified stones with 50 mg. indomethacin intravenously. Pain was relieved completely in 17 patients, while in 8 incomplete or no pain relief was achieved after the infusion of indomethacin. Patients completely relieved of pain had significantly higher levels of antidiuretic hormone in plasma before the infusion of indomethacin (18.2 plus or minus 3.4 pg./ml.) than patients with incomplete or no pain relief (7.2 plus or minus 1.3 pg./ml.) (p less than 0.01). These findings indicate that the volume status and/or the level of antidiuretic hormone may be of critical importance for pain relief after infusion of indomethacin in patients with ureteral colic. 0 (Vasopressins); 53-86-1 (Indomethacin); Herlitz H, Ahlmen J, Aurell M, Blohme I, Brynger H, Delin K et al. Captopril in hypertension after renal transplantation. Lancet 1983; 2(8363):1366-7. 147-85-3 (Proline); 62571-86-2 (Captopril); Herlitz H, Aurell M, Conradson T. Felodipine, an arteriolar dilator with pronounced antihypertensive effect. Lancet 1983; 1(8321):409-10. 0 (Antihypertensive Agents); 0 (Pyridines); 21829-25-4 (Nifedipine); 72509-76-3 (Felodipine); Herlitz H, Aurell M, Holm G, Granerus G, Schersten T. Renal degradation of insulin in patients with renal hypertension. Scand J Urol Nephrol 1983; 17(1):109-13. Renal processing of insulin was studied over plasma insulin levels of 5-80 mU/l by renal vein catheterization in 14 patients. Kidneys of patients with a normal GFR removed around 30% of the insulin from arterial plasma. In 6 patients having unilateral renal artery stenosis but only moderately impaired renal blood flow and unchanged PAH-extraction, a higher or unchanged fractional insulin extraction was seen in all but one, compared with the contralateral kidney. Due to the high fractional extraction of insulin by the kidneys with renal artery stenosis, a preserved total insulin uptake by these kidneys was seen. In 4 patients with renal hypoplasia (2 of them had renal artery stenosis) low values for insulin extraction and insulin uptake were seen on the affected side. One patient with chronic pyelonephritis and uremia had an extremely low renal insulin extraction and uptake. The results suggest that estimation of renal insulin extraction may be an important renal functional test in renovascular patients. 0 (Blood Glucose); 11061-68-0 (Insulin); Herlitz H, Ricksten SE, Lundin S, Thoren P, Aurell M, Berglund G. Renal denervation and sodium balance in young spontaneously hypertensive rats. Ren Physiol 1983; 6(3):145-50. In 7-week-old male, spontaneously hypertensive rats (SHR) and matched normotensive control rats, Wistar Kyoto Rats (WKY), a bilateral renal denervation was performed. In two additional groups of rats a sham denervation was done (SHRS, WKYS). The animals were then kept in metabolic cages during a 10-day period during which sodium intake, urine volume, urinary sodium excretion, fecal sodium excretion, urinary aldosterone excretion and plasma renin activity were determined. Fractional urinary excretion of sodium was higher in the denervated SHR (p less than 0.1) and WKY (p less than 0.05) during the first 3 days after denervation, but during the following 3-day periods no difference between denervated and sham-operated groups was noted. The difference in fractional urinary excretion of sodium initially was due to a diminished urinary sodium excretion in the sham-operated groups since both SHRS and WKYS exhibited a significant increase between the first and the last 3-day period. Urine volume increased significantly in both SHR and WKY after denervation. Urinary aldosterone excretion on the 7th day after denervation was significantly lower in SHR compared to WKY, but there was no significant difference between the denervated and sham-operated groups. PRA was also significantly lower in SHR but no significant decrease was seen after denervation. 52-39-1 (Aldosterone); 7440-23-5 (Sodium); Ljungman S, Aurell M, Hartford M, Wikstrand J, Berglund G. Effects of subpressor doses of angiotensin II on renal haemodynamics at different blood-pressure levels. Acta Med Scand Suppl 1983; 677:93-6. 11128-99-7 (Angiotensin II); Ljungman S, Aurell M, Hartford M, Wikstrand J, Berglund G. Effects of subpressor doses of angiotensin II on renal hemodynamics in relation to blood pressure. Hypertension 1983; 5(3):368-74. The renal hemodynamic response to subpressor doses of angiotensin II (AII; 0.1 and 0.5 ng/min/kg) was investigated in untreated 49-year-old men (n = 50) representing a wide blood pressure range. Renal blood flow, renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), plasma renin activity (PRA), plasma AII, plasma aldosterone, and the urinary excretion of sodium and norepinephrine were studied. The higher the initial blood pressure the greater was the increase in RVR in response to AII infusion (p less than 0.002), indicating an increased renal vascular reactivity with increase in initial blood pressure. The AII infusion gave a significant rise in RVR in both the borderline and hypertensive group, but gave no increase in RVR in the normotensive group, implying an enhanced sensitivity of the renal vasculature in the borderline and hypertensive group. The increase in RVR was greater in the hypertensive than in the borderline group, i.e., the hypertensives had a steeper dose-response curve than the borderline group, which points to the presence of structural vascular changes in the renal vessels in the hypertensives. The increase in RVR in response to AII was positively correlated to sodium intake and plasma aldosterone concentration, indicating that these two factors might modulate the renal vascular reactivity. These factors could, however, only partly explain that RVR increased more the higher the initial blood pressure. Thus, the results indicate that there is an increased reactivity of the renal vascular bed to AII in essential hypertension. The increased reactivity seems to be mediated through an increased sensitivity of the renal vasculature to AII in mild essential hypertension and also through the presence of structural vascular changes in established hypertension. These factors may lead to a reduced excretion of sodium and water and may therefore be of importance in the development and progression of essential hypertension. 11128-99-7 (Angiotensin II); 51-41-2 (Norepinephrine); 52-39-1 (Aldosterone); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Aurell M, Delin K, Herlitz H. Captopril in treatment-resistant essential and renal hypertension. Scand J Urol Nephrol 1982; 16(3):243-9. Captopril, an angiotensin converting enzyme inhibitor, was used to treat 25 patients with treatment-resistant hypertension of long duration. Seven patients had essential hypertension, 10 renovascular hypertension and 8 renoparenchymatous hypertension. All patients had GFR greater than 25 ml/min/1.73 m3 BSA. The acute blood-pressure-lowering response to the drug was shown to be dependent on the prevailing activity in the renin-angiotensin system. Its long-term effect was not correlated to the activation of the renin-angiotensin system as the mean blood-pressure decrease was not significantly different for high renin and normal renin patients (21 +/- 3% vs. 19 +/- 2%). All patients needed addition of diuretics and betablockers for optimum control. Nine patients have been well controlled for one year and several of them are now approaching two years' treatment. A few adverse effects were observed, including taste disturbances and increased proteinuria. The latter side effect occurred in two patients with decreased renal function and pre-existing proteinuria. Upon reduction of the dose the proteinuria returned to pre-treatment levels within a few months. We conclude that altogether 78% of these patients with treatment-resistant hypertension obtained greatly improved long-term blood-pressure control on treatment including captopril. 147-85-3 (Proline); 62571-86-2 (Captopril); Aurell M, Delin K, Herlitz H, Mulec H. Captopril treatment in hypertensive dialysis patients. Scand J Urol Nephrol 1982; 16(3):251-6. Captopril was used for treatment resistant arterial hypertension in 17 dialysis patients. Excellent blood-pressure control with diastolic blood-pressure less than 95 mmHg was obtained in 10 out of 17 patients (59%), with captopril as only drug in 8 patients. Six patients have been treated more than 6 months and 4 patients have been on the treatment for 1 year. The dosage of captopril could be kept low with maintained antihypertensive and angiotensin converting enzyme blocking effects. The acute blood-pressure lowering effect of captopril in dialysis patients was correlated to the initial plasma renin activity (p less than 0.001) but not long-term treatment, which was successful also in several low-renin patients. A few adverse reactions were encountered, e.g. urticaria and bullous exanthema, but all resolved when captopril treatment was stopped. Plasma potassium increased only from 4.8 +/- 0.1 to 5.0 +/- 0.1 mmol/l at the end of 1 month's treatment. Captopril appears to be a valuable drug for treatment of arterial hypertension in dialysis patients and offers an alternative to bilateral nephrectomy for the management of treatment resistant hypertension in these patients. 147-85-3 (Proline); 62571-86-2 (Captopril); EC 3.4.23.15 (Renin); Bratt CG, Aurell M, Erlandson BE, Nilson AE, Nilsson S. Intrapelvic pressure and urinary flow rate in obstructed and nonobstructed human kidneys. J Urol 1982; 127(6):1136-42. Adult; Aged; Comparative Study; Diuresis; Female; Glomerular Filtration Rate; Human; Hydronephrosis/physiopathology/radionuclide imaging; Kidney Concentrating Ability; Kidney Pelvis/physiopathology; Male; Middle Age; Pressure; Delin K, Aurell M, Granerus G, Holm J, Schersten T. Surgical treatment of renovascular hypertension in the elderly patient. Acta Med Scand 1982; 211(3):169-74. 0 (Antihypertensive Agents); EC 3.4.23.15 (Renin); Herlitz H, Lundin S, Henning M, Aurell M, Karlberg BE, Berglund G. Hormonal pattern during development of hypertension in spontaneously hypertensive rats (SHR). Clin Exp Hypertens A 1982; 4(6):915-35. Urinary excretion of sodium, noradrenaline, dopamine, aldosterone, prostaglandin E2 and plasma renin activity were determined in 7 and 16 weeks old spontaneously hypertensive rats (SHR) and in two normotensive control strains, ordinary Wistar control rats (NCR) and Wistar-Kyoto normotensive rats (WKR). Each group consisted of 10-11 rats. The animals were kept in metabolic cages. Experiments were performed on standard diet (5-8 mmol Na+/100 g food) and with an increased (15.6 and 56.0 mmol Na+/100 g food) salt intake. At 7 weeks of age, when SHR are in a borderline phase of hypertension, they exhibited a decreased urinary sodium excretion, and an increased urinary noradrenaline excretion compared to controls. The latter might reflect an increased overall activity of the sympathetic nervous system. Urinary dopamine excretion was also increased probably mirroring a higher activity in a renal natriuretic dopamine system. Plasma renin activity and urinary aldosterone excretion were depressed. At 16 weeks of age, when SHR are in an early establishment phase of hypertension, urinary sodium excretion was still lower in SHR, while urinary noradrenaline and dopamine excretions had become normal compared to controls. Plasma renin activity and urinary aldosterone excretion remained depressed. Urinary PGE2 excretion, only determined in this age group, was significantly higher in SHR. 0 (Hormones); 0 (Prostaglandins E); 363-24-6 (Dinoprostone); 51-41-2 (Norepinephrine); 51-61-6 (Dopamine); 52-39-1 (Aldosterone); 7440-23-5 (Sodium); 7647-14-5 (Sodium Chloride); EC 3.4.23.15 (Renin); Ljungman S, Aurell M, Hartford M, Wikstrand J, Berglund G. Blood pressure in relation to the renin-angiotensin-aldosterone system. Acta Med Scand 1982; 211(5):351-60. The relationship between blood pressure (BP) and the renin-angiotensin-aldosterone system was studied in a stratified random sample (n=120) of 49-year-old men selected from a BP screening and covering a wide range of BPs. Only subjects not on antihypertensive treatment were included. None had malignant or secondary hypertension. Plasma renin activity, plasma concentrations of angiotensin II, aldosterone, sodium, potassium and noradrenaline and the 24-hour urinary excretions of sodium, cortisol and noradrenaline were determined. Of these variables, only p-aldosterone was significantly correlated wtih BP, both in the whole study group (R=0.22, p less than 0.02, n=119) and in the subjects with the highest BP range (R=0.36, p less than 0.02, n=30). Of the clinical groups compared, the hypertensive subjects had significantly higher mean p-aldosterone than the borderline and normotensive subjects. Multiple regression analysis showed that the 24-hour urinary excretion of noradrenaline was the factor most strongly correlated to p-aldosterone, suggesting that the sympathetic nervous system might stimulate aldosterone secretion. Our findings indicate that aldosterone may be of importance for the development and maintenance of essential hypertension. 11128-99-7 (Angiotensin II); 52-39-1 (Aldosterone); EC 3.4.23.15 (Renin); Nyberg G, Granerus G, Aurell M. Renal extraction ratios for 51Cr-EDTA, PAH, and glucose in early insulin-dependent diabetic patients. Kidney Int 1982; 21(5):706-8. Renal clearances and extraction ratios for 51Cr-EDTA and PAH were studied in six young patients with insulin-dependent diabetes. The duration of the disease was 1 to 4 years, and no patient had signs of diabetic complications. Catheterization of the right renal vein and the left brachial artery was performed. The extraction ratios for 51Cr-EDTA, PAH, and glucose were determined at two different levels of blood glucose. Clearance for 51Cr-EDTA was increased by 9.7% and for PAH by 8.5% compared to normal control subjects while the extraction ratios for 51Cr-EDTA and PAH were normal. Extraction ratio for glucose was very low. There was no correlation between the individual HbA1 values and the clearances for 51Cr-EDTA and PAH. Extraction ratios for these substances were not influenced by acute changes in blood glucose level. The normal PAH extraction ratio indicates that PAH clearance is a reliable estimate of RPF in early insulin-dependent diabetes. 0 (Aminohippuric Acids); 0 (Blood Glucose); 0 (Chromium Radioisotopes); 11061-68-0 (Insulin); 60-00-4 (Edetic Acid); 61-78-9 (p-Aminohippuric Acid); 9034-51-9 (Hemoglobin A); Soubrier F, Devaux C, Galen FX, Skinner SL, Aurell M, Genest J et al. Biochemical and immunological characterization of ectopic tumoral renin. J Clin Endocrinol Metab 1982; 54(1):139-44. Biochemical and immunological characteristics of renin secreted by two malignant renin-secreting tumors [pulmonary (PT) and paraovarian (POT)] were studied. They both contain inactive renin (IR), as renin activity of tumoral extracts was able to be increased after acid activation or trypsin treatment (10.1 to 20.8 Goldblatt units/g tissue for PT and 1.4 to 3.71 for POT). Renin activity after activation reached the value obtained by direct RIA of human renin (23 and 3.4, respectively), as both forms are recognized by renin antiserum. Both enzymatic activities could be completely inhibited by renin antiserum. Displacement curves for the two tumoral renins paralleled the MRC renin in the direct RIA. After chromatography on affigel blue, active renin was not bound to the gel, and inactive renin eluted only with 1 M NaCl. On pepstatin A Sepharose and CBL-pepstatin Sepharose (an N-modified-pepstatin), a separation of the two forms of pulmonary renin was obtained; inactive renin eluted with breakthrough proteins, whereas active renin was strongly bound to the gel. After this affinity chromatography, the molecular weights of inactive and active renin, determined on Ultrogel, were very close (46,000 and 42,500). We conclude that 1) ectopic renin in these cases in similar to the renal enzyme; 2) renin can be secreted in an inactive form, supporting the hypothesis of an inactive initial state of renin; and 3) molecular weight differences between the two forms are very slight. EC 3.4.21.4 (Trypsin); EC 3.4.23.15 (Renin); Wallin L, Alling C, Aurell M. Impairment of renal function in patients on long-term lithium treatment. Clin Nephrol 1982; 18(1):23-8. A survey of the renal function in 278 patients on long-term lithium treatment maintained on plasma lithium concentration of 0.7-1.2 mmoles/l was conducted. The extent of renal damage were studied with urinary concentration tests, beta-2-microglobulin excretion and measurement of glomerular filtration rate. The mean treatment time was 6.5 years and the longest treatment time was 15 years. Forty-nine per cent of the patients could not concentrate their urine to above 800 mOsm/kg of water, which did not correlate with the presence of polyuria. The urine concentration capacity decreased as a function of time in the lithium treated group, and it was also influenced by the type of tablet administration (readily soluble or sustained release), but not by combination with other drugs, such as neuroleptics. Beta-2-microglobulin excretion was not increased. A reduced glomerular filtration rate was found in 17% and the filtration rate in the whole group of patients was clustered around the lower limit of normal. The filtration rate decreased as a function of the duration of treatment. It was found that the concentrating capacity and the filtration rate decreased in parallel and that there was no selective impairment of the concentrating capacity. We conclude that severe impairment of renal function is uncommon in well controlled patients. Urinary concentration tests are shown to be the most suitable test for detection of kidney damage in long-term lithium treatment. 0 (beta 2-Microglobulin); 7439-93-2 (Lithium); Aurell M, Delin K, Granerus G. Measures to increase the reliability in the diagnostics of renin dependent hypertension. Acta Med Scand Suppl 1981; 646:58-62. EC 3.4.23.15 (Renin); Aurell M, Ewald J. The use of living donors. Glomerular filtration rate during the first year after donor nephrectomy. Scand J Urol Nephrol Suppl 1981; 64:137-42. The functional increase in the remaining kidney after donor nephrectomy has two distinct components in man. There is a rapid initial increase in function within the first 24 hours, due to the circulatory adjustments in the kidney, but the mechanisms have not been elucidated. Thereafter, there is a further functional increase during the first year which in addition to the haemodynamic changes, also includes an increase in tubular function. The increased work-load on the kidney handling the increased volume of filtrate presented to the tubules may induce the increase in tubular function, but hormonal factors have been shown to contribute to the long-term increase in tubular function after contralateral nephrectomy. Adult; Glomerular Filtration Rate; Human; Hypertrophy/physiopathology; Kidney/pathology/physiology/transplantation; Kidney Transplantation; Middle Age; Nephrectomy; Postoperative Period; Tissue Donors; Aurell M, Rudin A. Effects of captopril in Bartter's syndrome. N Engl J Med 1981; 304(26):1609. 147-85-3 (Proline); 62571-86-2 (Captopril); Aurell M, Svalander C, Wallin L, Alling C. Renal function and biopsy findings in patients on long-term lithium treatment. Kidney Int 1981; 20(5):663-70. Nine patients on long-term lithium treatment (3 to 13 years) had abnormal renal function with a decreased GFR and/or a decreased maximal urinary concentration capacity. Four patients had received lithium as the only drug, whereas five patients had had concomitant treatment with neuroleptics. No patient had a history of nephrourological diseases. Abnormal renal morphology was present in the biopsy samples from all patients. Cortical fibrosis was found in a variable degree. Dilated tubules and microcysts in which the epithelial lining was clearly abnormal were found in majority of samples. Electron micrographically, two types of abnormal epithelial cells were observed, one with small elongated mitochondria with dense matrix and the other with large spherical and less dense mitochondria. In distal tubules, mitochondrial swelling, accumulation of cytosegrosomes, and nuclear pyknosis dominated the picture. These findings indicate a tubulointerstitial nephropathy and support the hypothesis that long-term lithium treatment may cause renal damage in susceptible patients. 7439-93-2 (Lithium); Bratt CG, Aurell M, Lindstedt G. Proximal tubular function in human hydronephrotic kidneys. J Urol 1981; 125(1):9-10. Proximal tubular was evaluated on the basis of the excretion rate of urinary beta-2-microglobulin of each kidney in 15 patients with unilateral hydronephrosis. Total and divided renal function was measured with 51chromium ethylenediaminetetraacetic acid clearance, isotope renography and a concentration test. Total renal function was normal in all patients. Parenchymal function, measured by renography, was reduced in 2 hydronephrotic kidneys and both patients had had upper urinary tract infections. The ability to concentrate urine was impaired in 10 hydronephrotic kidneys. These patients had renal calculi or had had upper urinary tract infections. The urinary beta-2-microglobulin excretion was normal in all hydronephrotic kidneys, indicating an intact proximal tubular function in these patients. 0 (beta 2-Microglobulin); Granerus G, Aurell M. Reference values for 51Cr-EDTA clearance as a measure of glomerular filtration rate. Scand J Clin Lab Invest 1981; 41(6):611-6. Reference values for glomerular filtration rate (GFR) were defined using eight reports including epidemiological studies and studies in kidney donors. Studies using both inulin and 51Cr-EDTA were included. GFR decreased with age, by 4 ml/min decade below the age of 50, and 10 ml/min decade above 50 years of age. No sex difference was found. +/- 2 SD was equal to 25 ml/min at all ages. Based on these findings a nomogram for GFR is presented. Emphasis is given to the use of plasma clearance of 51Cr-EDTA estimated with single injection technique as the new reference method for GFR measurement. 0 (Chromium Radioisotopes); 60-00-4 (Edetic Acid); Johnsen SA, Aurell M. Immunosuppressive action of captopril blocked by prostaglandin synthetase inhibitor. Lancet 1981; 1(8227):1005. 0 (Immunosuppressive Agents); 147-85-3 (Proline); 53-86-1 (Indomethacin); 62571-86-2 (Captopril); Kopp U, Aurell M, Sjolander M, Ablad B. The role of prostaglandins in the alpha- and beta-adrenoceptor mediated renin release response to graded renal nerve stimulation. Pflugers Arch 1981; 391(1):1-8. The role of prostaglandins in the renin release response to renal nerve stimulation (RNS) at different intensities was examined in the anaesthetized dog. The animals were divided into two groups receiving either low or high level RNS, defined by the frequencies of stimulation producing reduction in renal blood flow by 5% or less and 50%. Indomethacin or diclofenac sodium (5 mg/kg i.v.), prostaglandin synthesis inhibitors, did not affect the renin release response to low level RNS but decreased the renin release response to high level RNS by 31 +/- 8% (P less than 0.01). Addition of metoprolol, (0.5 mg/kg i.v.) beta-1-adrenoceptor antagonist, to indomethacin or diclofenac sodium resulted in a greater reduction (68 +/- 6% P less than 0.01) of the renin release response to high level RNS compared to that produced by either drug alone. Metoprolol, alone, reduced the renin release response to high level RNS by 37 +/- 14% (P less than 0.05). Phenoxybenzamine (0.6 microgram . kg-1 . min-1), alpha-adrenoceptor antagonist, into the renal artery practically abolished the renal vasoconstrictor response to high level RNS and reduced the renin release response by 50 +/- 7% (P less than 0.01). Addition of metoprolol to phenoxybenzamine practically abolished the renal vasoconstrictor response and the renin release response to high level RNS; 94 +/- 4% (P less than 0.01). Addition of phenoxybenzamine to indomethacin or diclofenac sodium practically abolished the renal vasoconstrictor response to high level RNS but did not produce any greater reduction of the renin release response than that produced by either drug alone. These findings suggest that low level RNS results in renin release which is not dependent on prostaglandins. High level RNS results in renin release which is partly mediated by beta-1-adrenoceptors and partly related to alpha-adrenoceptors mediated renal vasoconstriction. Prostaglandins are not involved in the renin release deriving from alpha-adrenoceptor mediated renal vasoconstriction. 0 (Drug Combinations); 0 (Prostaglandins); 0 (Receptors, Adrenergic); 0 (Receptors, Adrenergic, alpha); 0 (Receptors, Adrenergic, beta); 15307-86-5 (Diclofenac); 37350-58-6 (Metoprolol); 53-86-1 (Indomethacin); 59-96-1 (Phenoxybenzamine); EC 3.4.23.15 (Renin); Kopp U, Aurell M, Svensson L, Ablad B. Effect of prenalterol, a beta-1-adrenoceptor agonist, on renin secretion rate in the anaesthetized dog. Acta Pharmacol Toxicol (Copenh) 1981; 49(3):230-5. The effects of the beta-1-adrenoceptor agonist, prenalterol, 20 microgram/kg intravenously on renin secretion rate (RSR), renal haemodynamics and sodium excretion were examined in anaesthetized dogs with innervated or denervated kidneys. In dogs with innervated kidneys, prenalterol increased RSR from 1.1 +/- 0.2 to 7.9 +/- 0.1 units X min.-1 X g-1 (P less than 0.01). Prenalterol did not affect mean arterial pressure, renal blood flow, glomerular filtration rate or sodium excretion. Heart rate was increased by 53 +/- 17 beats/min. (P less than 0.01). The increase in RSR produced by prenalterol was independent of intact renal innervation as RSR increased to the same extent in dogs with denervated kidneys. Pretreatment with the beta-1-adrenoceptor antagonist, metoprolol 0.5 mg/kg intravenously, abolished the increase in RSR produced by prenalterol. These findings suggest that prenalterol directly activates renal beta-1-adrenoceptors to increase RSR. 0 (Adrenergic beta-Agonists); 37350-58-6 (Metoprolol); 57526-81-5 (Prenalterol); 6673-35-4 (Practolol); EC 3.4.23.15 (Renin); Ljungman S, Aurell M, Hartford M, Wikstrand J, Berglund G. Blood pressure and the renin--angiotensin--aldosterone system. Clin Sci (Colch) 1981; 61 Suppl 7:261s-3S. The relationships between blood pressure and the components of the renin--angiotensin--aldosterone system were studied in 49-year-old men (n = 120) who were selected at random from the total population so as to be representative of all blood pressure levels. 2. Only plasma aldosterone concentration was significantly correlated with blood pressure, both in the whole study group (r = 0.22; P less than 0.02) and in the hypertensive blood pressure range (r = 0.36; P less than 0.02). The hypertensive subjects had a significantly higher plasma aldosterone concentration than the borderline and normotensive subjects. 3. Multiple regression analysis including factors related to the renin--angiotensin--aldosterone system, showed that the 24 h urinary excretion of noradrenaline was the factor most strongly correlated to plasma aldosterone. 4. The findings indicate that aldosterone may be the most important component of the renin--angiotensin--aldosterone system in the development and maintenance of essential hypertension. 11128-99-7 (Angiotensin II); 52-39-1 (Aldosterone); EC 3.4.23.15 (Renin); Ljungman S, Aurell M, Hartford M, Wikstrand J, Wilhelmsen L, Berglund G. Sodium excretion and blood pressure. Hypertension 1981; 3(3):318-26. 7440-09-7 (Potassium); 7440-23-5 (Sodium); Wilhelmsen L, Bjure J, Ekstrom-Jodal B, Aurell M, Grimby G, Svardsudd K et al. Nine years' follow-up of a maximal exercise test in a random population sample of middle-aged men. Cardiology 1981; 68 Suppl 2:1-8. A stepwise bicycle exercise test up to maximum was performed in a random population sample of 793 Swedish men, all aged 54 years. High respiratory rate during exercise characterized those who later suffered myocardial infarction (MI) or sudden coronary death (SD). In addition to high cholesterol, high blood pressure (BP), and smoking, low maximal performance, but not ST changes during exercise, increased the risk of MI + SD also in multivariate analysis. Pulse rate, systolic BP at both submaximal and maximal work load were positively correlated with the initial blood pressure level. BP at these work loads was also positively correlated with subsequent BP increase. 57-88-5 (Cholesterol); Bjure J, Aurell M, Granerus G, Haugstvedt S. Methodological aspects of renography in children. Scand J Urol Nephrol 1980; 14(3):243-50. Kidney function in children by renography has been evaluated. For reproducible results a high degree of standardization with respect to position, hydration and dosage was necessary. The wide range of kidney size and depth in children requires age-adapted collimators. For practical use for different size have been constructed for the age-groups: less 1 year, 1-5 years, 6-9 years and 10-15 years. A reduction in the surrounding activity of the kidneys is thereby obtained and disturbing influence from the bladder or contralateral kidney is prevented. Kidney function variables from the renogram are presented in terms of uptake and excretion ratios. The correlation between sum of uptake ratios and clearance measurements is good in cases with slight or moderate difference in kidney size. The standardized renographic technique has many advantages for kidney function measurements in children. The method is applicable in all ages, it is simple and reliable without extensive preparations and requires a low radiation dose. Also in children we can confirm the previous opinion obtained in adults that renography is a clinical valuable method of measuring kidney function. Adolescence; Adult; Child; Child, Preschool; Glomerular Filtration Rate; Human; Infant; Kidney/physiology/physiopathology; Kidney Diseases/physiopathology; Radioisotope Renography/instrumentation/methods; Reference Values; Time Factors; Granerus G, Aurell M, Bjure J, Haugstvedt S, Ljung B. Evaluation of unilateral kidney function in children. A comparison between renography and separate clearance. Scand J Urol Nephrol 1980; 14(3):263-7. Unilateral kidney function in children was evaluated by determination of 51Cr-EDTA-clearance combined with estimation of side distribution of kidney function by renography. As reference, separate clearance of 51Cr-EDTA, determined by sequential external ureteral occlusions on both sides, was used. A comparison between these two methods was made in 28 patients with varying degrees of unilateral kidney function impairment. A significant correlation was found when the renograms were corrected for extrarenal background activity. Thus, renography in combination with determination of the glomerular filtration rate with 51Cr-EDTA is a valuable method for evaluating separate kidney function in children, both methods being easily performed and requiring small radiation doses. 0 (Chromium Radioisotopes); 60-00-4 (Edetic Acid); Hoffmann KJ, Regardh CG, Aurell M, Ervik M, Jordo L. The effect of impaired renal function on the plasma concentration and urinary excretion of metoprolol metabolites. Clin Pharmacokinet 1980; 5(2):181-91. Plasma concentration and urinary excretion of total and 2 active metabolites of metoprolol have been studied in patients with varying degrees of renal impairment and in healthy subjects after intravenous and oral administration of 20 and 50 mg of 3H-metoprolol tartrate respectively. Renal clearance of total metabolites correlated directly with 51Cr-EDTA clearance (r = 0.95, p less than 0.001). A reduction of glomerular filtration rate (GFR) by 70 to 80% increased the elimination half-life of total metabolites and of the active metabolite alpha-hydroxymetoprolol about 3-fold. Significant accumulation was, however, only observed in the patients with a GFR of about 5 ml/min. Even in these patients, the contribution of alpha-hydroxymetoprolol to the beta-adrenoceptor blocking effect of metoprolol will be negligible. The second active metabolite studied is eliminated via biotransformation, and the urinary excretion as well as the plasma concentration of this metabolite were extremely low in comparison with those of the parent drug. 0 (Propanolamines); 37350-58-6 (Metoprolol); Jordo L, Attman PO, Aurell M, Johansson L, Johnsson G, Regardh CG. Pharmacokinetic and pharmacodynamic properties of metoprolol in patients with impaired renal function. Clin Pharmacokinet 1980; 5(2):169-80. The pharmacokinetics of metoprolol have been studied in a group of patients with varying degrees of renal impairment and in healthy subjects after administration of 20 mg of metoprolol tartrate intravenously and 50 mg orally in a single dose and during steady-state conditions. There were no significant differences in the extent of bioavailability or rate of elimination of the drug between the 2 groups. The fraction of the oral dose systemically available during steady-state was 59 +/- 9% in the renal patients and 55 +/- 7% in the control group. Total body clearance in the patients with renal failure was 1.0 +/- 0.1 L/min and in the healthy subjects it was 0.8 +/- 0.1 L/min. The corresponding values for the elimination half-life were 4.6 +/- 1.2h and 4.1 +/- 1.0h, respectively. The beta-adrenoceptor blocking effect of metoprolol (determined as percent reduction of exercise heart rate) did not differ significantly between the 2 groups during steady-state conditions. The effect on exercise heart rate was linearly related to the log of the plasma concentration of metoprolol. The relationship was identical for the single dose and during steady-state conditions, indicating that accumulation of metabolites in patients with renal failure does not influence the beta-blocking properties of metoprolol. 0 (Adrenergic beta-Antagonists); 0 (Propanolamines); 37350-58-6 (Metoprolol); Kopp U, Aurell M, Nilsson IM, Ablad B. The role of beta-1-adrenoceptors in the renin release response to graded renal sympathetic nerve stimulation. Pflugers Arch 1980; 387(2):107-13. The contribution of beta-adrenoceptor activation to renin release was examined in anaesthetized dogs using renal nerve stimulation (RNS) at different discharge rates in the presence of i.v. beta-adrenoceptor blockade. The animals were divided into 2 groups, which received either low or high level of RNS, defined by the frequency of stimulation producing decrease in renal blood flow of 5 and 50%, respectively. Low level RNS increased renin release tenfold. The renin release response was almost abolished by 0.5 mg/kg of metoprolol or dl-propranolol but unaffected by 0.5 mg/kg of d-propranolol. The increase in renin release to high level RNS was equally reduced by 33% by 0.5 mg/kg and 2.0 mg/kg of metoprolol. dl-propranolol, 0.5 mg/kg, reduced the renin release response to about the same extent, 44%, while 2.0 mg/kg reduced it somewhat more, 59%. This was probably due to its membrane stabilizing properties as d-propranolol, 2.0 mg/kg and lidocaine 2.0 mg/kg + 0.1 mg x kg-1 x min-1, also reduced the renin release response. These data suggest that the renin release response to low level RNS is almost completely mediated by beta-adrenoceptors which are of the beta-1 subtype. High level RNS results in a renin release, which is only partly mediated by beta-1-adrenoceptors. The remainder is apparently related to other mechanisms activated by high level RNS and is probably a consequence of the associated renal vasoconstriction. 0 (Adrenergic beta-Antagonists); 0 (Receptors, Adrenergic); 0 (Receptors, Adrenergic, beta); 137-58-6 (Lidocaine); EC 3.4.23.15 (Renin); Ljungman S, Aurell M, Hartford M, Wikstrand J, Wilhelmsen L, Berglund G. Blood pressure and renal function. Acta Med Scand 1980; 208(1-2):17-25. The relationship between blood pressure (BP) and renal function was studied in samples of 49-year-old men. Of 3 205 49-year-old men, 2 376 (74%) took part in a BP screening. By systematic sampling, based on diastolic BP levels varying from very low to very high, 120 subjects were selected for this study. Only subjects who were not on antihypertensive treatment were included. Renal blood flow (RBF), renovascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF) and renal concentrating capacity were studied in 111 subjects, none of whom had advanced hypertension. With increasing BP there was a decrease in RBF (r = -0.34) and an increase in RVR (r = 0.81) and FF (r = 0.35). The changes in renal haemodynamics occurred gradually from low to high BP, and did not start at any particular BP level. With increasing BP, GFR was unchanged. An "autoregulation of GFR" was thus found at all BP levels studied. Renal concentrating capacity was unchanged. These findings indicate that renal haemodynamics in essential hypertension are adjusted mainly to ensure a constant GFR. Blood Pressure; Glomerular Filtration Rate/methods; Heart Rate; Hematocrit; Human; Kidney/blood supply/physiology; Kidney Concentrating Ability; Kidney Function Tests/methods; Male; Middle Age; Regional Blood Flow; Sweden; Vascular Resistance; Nilson AE, Aurell M, Bratt CG, Nilsson S. Diuretic urography in the assessment of obstruction of the pelvi-ureteric junction. Acta Radiol Diagn (Stockh) 1980; 21(4):499-503. Twenty adult patients with urographic evidence of unilateral, moderately wide renal pelves were examined by routine and diuretic urography. Planimetry of the corresponding calyx system of the two examinations was performed. An increase in size by more than 20 per cent following osmotic diuresis indicated an obstruction of the pelvi-ureteric junction in kidneys with moderately wide renal pelves. Diuretic urography may be useful to diagnose obstruction as a cause of moderately wide renal pelves and to assess operative results. 0 (Contrast Media); 0 (Diuretics); 1949-45-7 (Metrizoate); 69-65-8 (Mannitol); 7241-11-4 (isopaque cerebral); Aurell M. Fibromuscular dysplasia of the renal arteries. Br Med J 1979; 1(6172):1180-1. Two cases of severe fibromuscular dysplasia of the renal arteries are described in which the diagnosis was made 12 and 11 years after renal angiography had shown the arteries to be normal. The discovery of hypertension preceded the diagnosis by two and 11 years respectively, and in one case hypertension was present at the time of the normal renal angiogram. The report suggests that fibromuscular dysplasia of the renal arteries is acquired and may not be present from birth. The importance of regular review in cases of severe hypertension is emphasised. Adult; Arterial Occlusive Diseases/complications; Case Report; Female; Fibromuscular Dysplasia/complications/radiography; Human; Hypertension, Renovascular/radiography; Middle Age; Renal Artery/radiography; Renal Artery Obstruction/radiography; Aurell M, Delin K, Ewald J. Urinkoncentrationsprov med vasopressin-analogen DDAVP. Lakartidningen 1979; 76(21):2045-6. English title: "Urine concentrating ability test with the vasopressin analog DDAVP" 0 (Vasopressins); Aurell M, Hestbech J. Lithium-induced uraemia. Lancet 1979; 1(8121):882. 7439-93-2 (Lithium); Aurell M, Lincoln K, Bucht H. Bakampicillin vid urinvagsinfektioner. Lakartidningen 1979; 76(21):2051-2. English title: "Bakampicillin in urinary tract infections" 69-53-4 (Ampicillin); Aurell M, Rudin A, Tisell LE, Kindblom LG, Sandberg G. Captopril effect on hypertension in patient with renin-producing tumour. Lancet 1979; 2(8134):149-50. 0 (Enzyme Inhibitors); 0 (Hormones, Ectopic); 147-85-3 (Proline); EC 3.4.15.1 (Peptidyl-Dipeptidase A); EC 3.4.23.15 (Renin); Delin K, Aurell M, Bendz H. Assessment of renal concentrating ability. Br Med J 1979; 1(6167):888-9. 113-79-1 (Argipressin); 16679-58-6 (Desmopressin); Herlitz H, Aurell M, Granerus G. Cyclic AMP, renal function and dihydralazine-stimulated renin secretion in hypertensive patients. Scand J Clin Lab Invest 1979; 39(4):303-9. The concentrations of plasma cAMP and plasma renin activity were determined in arterial and renal venous plasma in nineteen patients investigated for renin-mediated hypertension. The cAMP measurements were performed in two different situations (1) under basal conditions and (2) after i.v. dihydralazine administration, a potent renin stimulation procedure. Thirteen patients had a lateralization of the renin secretion in the basal state and the administration of dihydralazine caused a further marked renin-secretion. The cAMP concentration was higher in the renal veins draining renin-positive kidneys than in the contralateral renal veins. No significant change was observed between the arterial cAMP concentration and the cAMP concentration in either of the renal veins during dihydralazine-stimulated renin secretion. There was no correlation between the cAMP extraction and the renin secretion of the individual kidneys, but the cAMP extraction correlated with the extraction ratio of PAH. These results show that cAMP values are mainly influenced by the renal function and are not related to the state of renin secretion. Increased cAMP levels in renovascular patients and urameic patients are therefore mainly due to defective elimination of the nucleotide by the kidneys. 484-23-1 (Dihydralazine); 60-92-4 (Cyclic AMP); 61-78-9 (p-Aminohippuric Acid); 86-54-4 (Hydralazine); EC 3.4.23.15 (Renin); Herlitz H, Lundin S, Ricksten SE, Gothberg G, Aurell M, Hallback M et al. Sodium balance and structural vascular changes in the kidney during development of hypertension in spontaneously hypertensive rats. Acta Med Scand Suppl 1979; 625:111-5. 7440-23-5 (Sodium); Hestbech J, Aurell M. Lithium-induced uraemia. Lancet 1979; 1(8109):212-3. 7439-93-2 (Lithium); Ljungman S, Hartford M, Aurell M, Berglund G. Pathophysiological mechanisms of the antihypertensive effect of a cardioselective beta-adrenoceptor blocking drug (metoprolol). Acta Med Scand Suppl 1979; 625:31-5. 0 (Propanolamines); 37350-58-6 (Metoprolol); 51-41-2 (Norepinephrine); 52-39-1 (Aldosterone); EC 3.4.23.15 (Renin); Nilsson S, Aurell M, Bratt CG. Maximum urinary concentration ability in patients with idiopathic hydronephrosis. Br J Urol 1979; 51(6):432-6. The maximum urinary concentration ability and renal parenchymal function of each kidney were investigated in 34 patients with unilateral hydronephrosis. The ability to concentrate urine was not reduced in 10 hydronephrotic and 24 contralateral kidneys. The concentration ability was moderately reduced in 14 hydronephrotic and 10 non-hydronephrotic kidneys and severely impaired in 10 hydronephrotic kidneys. A reduced concentration ability was found almost entirely in hydronephrosis complicated with upper urinary tract infection or renal calculi. Hydronephrotic kidneys without these complications showed a normal concentration ability in 10 of 11 cases. Parenchymal function was reduced in only 10 hydronephrotic kidneys, 7 of which had had upper urinary tract infections and 3 of which had renal stones. It is our opinion that uncomplicated cases of unilateral hydronephrosis should not be operated upon unless necessitated by signs and symptoms. Measurement of the maximum urinary concentration ability might be helpful in setting the correct indication for surgery in borderline cases. Adult; Female; Human; Hydronephrosis/complications/physiopathology; Kidney Calculi/complications; Kidney Concentrating Ability; Male; Middle Age; Urinary Tract Infections/complications; Rudin A, Aurell M, Hansson L, Westberg G. Effect of Sar1-ala8-angiotensin II on blood pressure and renin in Bartter's syndrome, before and after treatment with prostaglandin synthetase inhibitors. Scand J Clin Lab Invest 1979; 39(6):543-50. Three patients suffering from Bartter's syndrome were studied before and after 5 days of treatment with the prostaglandin synthetase inhibitors, aspirin and indomethacin. Saralasin was given by intravenous infusion in increasing doses from 0.6 to 42 micrograms/min.kg/BW. During saralasin infusion a blood pressure reduction was observed in all patients. Aspirin treatment did not affect this response and nor did it affect other manifestations of the syndrome. Indomethacin treatment changed the blood pressure response to saralasin in such a way that the blood pressure was increased in one patient and was unchanged in the other. Indomethacin also tended to normalize other features of Bartter's syndrome, such as the hyperreninaemia and angiotensin unresponsiveness, but did not affect the hypokalaemia. The saralsin effect on blood pressure is thus evidently inversely related to the prevailing activity of the renin-angiotensin system in this condition also, and the patients obviously depended on the renin-angiotensin system to maintain their blood pressure. Our findings, together with data in the literature, indicate that angiotensin unresponsiveness of the vascular bed is not a primary feature in Bartter's syndrome. Chloride loss is currently thought to be the basic abnormality and this may link the Bartter's syndrome with other diseased states characterized by chloride loss, such as the syndrome of habitual vomiting and chronic treatment with loop diuretics. 0 (Electrolytes); 0 (Prostaglandins); 11128-99-7 (Angiotensin II); 34273-10-4 (Saralasin); 50-78-2 (Aspirin); 53-86-1 (Indomethacin); EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthase); EC 3.4.23.15 (Renin); Aurell M, Delin K, Granerus G. Observations on the use and limitations of renal vein renins in hypertensive patients. Contrib Nephrol 1978; 11:146-9. From our consecutive series of renal vein renin studies in 170 patients with kidney disorders and hypertension, we present those cured by surgical correction of a unilateral renal artery stenosis during the period 1973--75. The renin secretion patterns of these patients range between no demonstrable abnormality, even with a stimulating procedure using dihydralazine 7.5 i.v., and massive renin secretion already during basal conditions. Thus, the renin secretion may not be increased even after stimulation in some patients with durable unilateral renovascular hypertension. This fact may be explained by the rise of the systemic blood pressure, eventually maintained by sodium and water retention and accompanied by adaptive changes in the contralateral kidney. The perfusion pressure is thereby kept normal in the affected kidney, eliminating a stimulus for renin secretion. It is likely that many cases of renovascular hypertension pass through an early stage where no involvement of the renin-angiotensin system may be discovered. Of course, these patients will also benefit from surgery. The conclusion is that renin studies for diagnostic purposes should be performed when patients are on treatment and kept normotensive for some time, and that an additional challenge of the perfusion pressure, i.e., by use of dihydralazine, intravenously should be performed. EC 3.4.23.15 (Renin); Aurell M, Fritjofsson A, Granerus G, Grimby G. Renal extraction of p-aminohippurate: physiological and clinical observations. Contrib Nephrol 1978; 11:14-8. 0 (Aminohippuric Acids); 61-78-9 (p-Aminohippuric Acid); Bratt CG, Aurell M, Nilson A, Nilsson S. Diuretic urography and renography in the diagnosis of hydronephrosis. Contrib Nephrol 1978; 11:142-5. 0 (Diuretics, Osmotic); Delin K, Aurell M, Ewald J. Urinary concentration test with desmopressin. Br Med J 1978; 1(6115):757-8. 0 (Vasopressins); 16679-58-6 (Desmopressin); Jagenburg R, Attman PO, Aurell M, Bucht H. Determination of glomerular filtration rate in advanced renal insufficiency. Scand J Urol Nephrol 1978; 12(2):133-7. The glomerular filtration rate (GFR) has been determined in 17 patients with advanced renal insufficiency (GFR less than 15 ml/min) by different clearance techniques using creatinine, inulin and 51Cr-EDTA as filtration markers. With renal inulin clearance as reference method for GFR, endogenous renal creatinine clearance overestimated GFR by an average of 30%. Renal clearance of 51Cr-EDTA and inulin were closely correlated and thus 51Cr-EDTA is a suitable GFR marker even at low filtration rates. However, it was found that the plasma clearance of 51Cr-EDTA overestimated the GFR often by more than 100% in the range 2.6--11.2 ml/min. Renal clearance measured during 24 h was lower than 4 h renal clearance with the patient well hydrated and resting in bed. It is concluded that the precise measurement of low glomerular filtration rates requires the use of renal clearance techniques. Four-hour 51Cr-EDTA renal clearance is a suitable method for measuring and following the development of renal function in advanced renal insufficiency. 0 (Chromium Radioisotopes); 60-00-4 (Edetic Acid); 60-27-5 (Creatinine); 9005-80-5 (Inulin); Bratt CG, Aurell M, Nilsson S. Renal function in patients with hydronephrosis. Br J Urol 1977; 49(4):249-55. The glomerular filtration rate and pelvic drainage function were reinvestigated after 3-5 years in 50 patients with hydronephrosis secondary to functional obstruction in the pelvic-ureteric junction. Pyeloplasty by the Anderson-Hynes' technique had been performed in 28 kidneys, while 12 patients were not operated upon and 10 had had a nephrectomy. The glomerular filtration rate was determined with the clearance technique and isotope renography. 16 out of 28 kidneys subjected to pyeloplasty and 11/12 non-operated kidneys had a normal renal parenchymal function at the first investigation in spite of severely disturbed drainage function. In the non-operated series the renal parenchymal function was unchanged in 11 patients. Deterioration was observed in 1 kidney, probably because of chronic pyelonephritis. Uncomplicated cases of pelvic-ureteric junction obstruction should not be operated upon unless necessitated by symptoms. A yearly control programme including a renal function test and plain films of the upper urinary tract is recommended for these patients. Adult; Glomerular Filtration Rate; Human; Hydronephrosis/physiopathology/ surgery; Kidney/physiopathology; Middle Age; Radioisotope Renography; Delin K, Aurell M, Granerus G. Renin-dependent hypertension in patients with unilateral kidney disease not caused by renal artery stenosis. Acta Med Scand 1977; 201(4):345-51. The practical value of renin secretion studies in hypertension associated with unilateral kidney disease, other than renal artery stenosis, has not been documented. This study, comprising 19 patients of this kind, disclosed three who had an abnormal renin secretion from the diseased kidney. The level of peripheral renin under basal conditions, and the change from this level as a result of provocation of renin secretion, were used to evaluate the importance of an arteriovenous renin gradient in the diseased kidney. The three patients were the only ones to become normotensive when the diseased kidney was removed in seven of the cases studied. When nephrectomy is considered in severe hypertension with unilateral kidney disease, there is a place for renin secretion studies, but a screening procedure is advisable. Measuring peripheral renin under basal conditions and after provocation of renin secretion, should reveal whether the renin-angiotensin system might be playing a part in maintaining the high BP. The finding of diminishing kidney function in many of the patients, despite good BP control, emphasizes the importance of sparing kidney function whenever possible. EC 3.4.23.15 (Renin); Aurell M. Renin--angiotensin-systemet hos normo- och hypertoniker. Lakartidningen 1976; 73(43):3658-9. English title: "The renin-angiotensin system in normal and hypertensive individuals" 11128-99-7 (Angiotensin II); EC 3.4.23.15 (Renin); Berglund G, Aurell M, Wikstrand J, Wallentin I. Plasma renin activity and hypertensive organ manifestations in 50-year-old males. Acta Med Scand 1976; 199(4):243-9. From a screening examination in a randomly selected third of the 50-year-old male population in Goteborg, Sweden, a 10% subsample was selected as a reference group (n=80). All untreated persons with SBP greater than 175 or DBP greater than 115 mmHg on two separate occasions made up the hypertension group (n=35). The reference group and the hypertension group were subjected to the same investigations, including BP measurement before and after rest and determination of plasma renin activity (PRA), urinary sodium and norepinephrine excretion and GFR. Plasma renin activity was approximately normally distributed in both the reference and the hypertension group. Mean values were 0.78 +/- 0.18 and 0.65 +/- 0.17 ng/ml/h respectively, the difference being almost statistically significant (0.10 greater than p greater than 0.05). There was no difference with respect to sodium excretion between the reference group and the hypertension group. In the reference group, heart rate was positively correlated to PRA and to urinary norepinephrine excretion during the day. No linear correlation between PAR and BP was found, either in the reference group, or in the hypertension group. Sodium excretion during the day was positively correlated to GFR in the hypertension group, but not in the reference group. Compared to hypertensives with normal or high sodium excretion during the day, the hypertensives with low sodium excretion during the day were characterized by a higher BP, a lower GFR and a reversed diurnal rhythm of urine excretion. Thus, low sodium excretion seemed to indicate more severe hypertension with increased renal resistance during the day. The hypertension group was also divided with regard to sodium excretion into a low, normal and high renin group. The low renin group had the lowest GFR and with rising renin group (from low via normal to high) there was a significant increase in GFR and a significant decrease in resting BP. The results indicate that low renin hypertension is not a more mild, but indeed rather a more severe form of hypertension. 51-41-2 (Norepinephrine); 7440-23-5 (Sodium); EC 3.4.23.15 (Renin); Berglund G, Aurell M, Wilhelmsen L. Renal function in normo- and hypertensive 50-year-old males. Acta Med Scand 1976; 199(1-2):25-32. Renal function, measure as glomerular filtration rate (GFR), sodium excretion and osmolality after thirst, has been determined in untreated (n=35) and treated (n=22) hypertensives and in a reference group (n=80), all derived from a random population sample of 50-year-old men. Renal function was related to casual and resting BP and to relative body weight. Hypertension was defined as SBP greater than 175 or DBP greater than 115 mmHg on two separate occasions or current antihypertensive treatment. Mean GFR was 100 +/- 11.7 ml/min in the reference group and significantly lower, 94 +/- 15.7 ml/min, in the hypertension group. In the hypertension group, 20% had a reduced GFR, although the standard diagnostic procedure, serum creatinine, demonstrated only 4%. Hypertensives with reduced GFR were characterized by higher BP, lower urinary sodium excretion, reversed diurnal rhythm of salt and water excretion and a higher relative body weight, which was, however, explained by the correlation of BP to relative body weight. GFR was negatively correlated to DBP at rest and positively correlated to urinary sodium excretion. Untreated hypertensives with persistent high BP after rest and lower GFR, lower urinary sodium excretion and reversed diurnal rhythm of salt and water excretion, indicating high renal resistance. The results suggest that subjects with relatively severe hypertension as judged by BP and renal function have an increased renal vascular resistance. 7440-23-5 (Sodium); Delin K, Aurell M, Claes G, Teger-Nilsson AC, Wallentin I. Multiple arterial occlusions and hypertension probably caused by an oral contraceptive: a patient in whom the development of renovascular hypertension has been followed. Clin Nephrol 1976; 6(4):453-7. An 18-year-old woman taking an oral contraceptive was admitted to hospital because of a stroke due to occlusion of three branches of the right middle cerebral artery. She later developed renovascular hypertension due to occlusion of one of two renal arteries on the right side. Occlusion of the ceoliac artery was also found. The circumstances suggest that the occlusions were caused by multiple emboli, the source of which could not be identified. The kidney with the circulatory disturbance was shown to have a persistent abnormal renin secretion three and six months after the stroke, but the peripheral renin level was lower at the second investigation. Cardiac function studies revealed an alarming degree of left ventricular hypertrophy, and satisfactory blood pressure control could not be maintained despite increasing antihypertensive therapy. Surgical corrrction of the circulatory disturbance promptly led to normotension without drugs, and the patient has remained normotensive during the postoperative observation period of twelve months. The oral contraceptive was probably responsible for precipitating the vascular occlusions, but no predisposing factors or warning symptoms were present to identify this patient as being at risk. 0 (Contraceptives, Oral); 0 (Contraceptives, Oral, Combined); 3562-63-8 (Megestrol); 57-63-6 (Ethinyl Estradiol); Ljungman S, Hartford M, Aurell M, Berglund G, Wikstrand J. Renal function and renovascular resistance in essential hypertension. Acta Med Scand Suppl 1976; 602:82-7. 51-41-2 (Norepinephrine); Werko L, Aurell M, Johnsson G, Sannerstedt R, Svedmyr N. Studies with a new cardioselective beta-blocker, metoprolol. Adv Clin Pharmacol 1976; 11:19-25. These studies indicate that the cardioselective beta-adrenergic blocking drug metoprolol might be expected to be at least as effective for the treatment of arterial hypertension as propranolol. The difference in effect on the peripheral vascular bed may be of importance when acute increase of the blood adrenaline level occur, as in severe anxiety states. Experience in long-term studies in all kinds of patients with raised arterial pressure has confirmed that metoprolol is an active antihypertensive agent of similar potency to other beta-blocking agents. 0 (Propanolamines); 37350-58-6 (Metoprolol); 51-43-4 (Epinephrine); 525-66-6 (Propranolol); EC 3.4.23.15 (Renin); Wilhelmsen L, Tibblin G, Aurell M, Bjure J, Ekstrom-Jodal B, Grimby G. Physical activity, physical fitness and risk of myocardial infarction. Adv Cardiol 1976; 18(0):217-30. Exercise Test; Exertion; Follow-Up Studies; Hemodynamics; Human; Male; Middle Age; Myocardial Infarction/epidemiology/mortality; Physical Fitness; Prognosis; Smoking; Sweden; Attman PO, Aurell M, Johnsson G. Effects of metoprolol and propranolol on furosemide-stimulated renin release in healthy subjects. Eur J Clin Pharmacol 1975; 8(3-4):201-4. The effects of single doses of the beta1-receptor antagonist metoprolol (40 mg orally), propranolol (40 mg orally) and placebo were compared on furosemide-stimulated plasma renin activity (PRA) in seven healthy subjects. In the placebo studies, PRA increased by 0.59+/-0.18 ng x ml-1 x h-1 60 minutes after intravenous administration of 30-60 mg furosemide. After propranolol and metoprolol, the corresponding increases in PRA were significantly less pronounced amounting to 0.16+/-0.06 and 0.24+/-0.08 ng x ml-1 x h-1, respectively. The resting heart rate was reduced to the same extent after the two beta-blockers, which means that the two drugs had been given in equipotent beta1-receptor blocking doses. It is suggested that the release of renin from the kidney may partly be mediated via an adrenergic beta1-receptor. 0 (Placebos); 525-66-6 (Propranolol); 54-31-9 (Furosemide); EC 3.4.23.15 (Renin); Aurell M, Bjure J, Ekstrom-Jodal B, Grimby G, Tibblin G, Wilhelmsen L. Arbetsprovets prediktiva formaga hos "1913 ars man". Lakartidningen 1975; 72(5):345-7. English title: "Predictive value of the work test in men born in 1913" Blood Pressure; Electrocardiography; Exercise Test; Heart Rate; Human; Male; Middle Age; Myocardial Infarction/diagnosis; Oxygen Consumption; Respiration; Spirometry; Aurell M, Pettersson M, Berglund G. Renin-angiotensin system in essential hypertension. Lancet 1975; 2(7930):342-5. In a random sample of normotensive and hypertensive fifty-year-old men plasma-renin-activity (P.R.A.), plasma-renin-concentration (P.R.C.), and renin substrate were measured using radioimmunoassay for angiotensin I. P.R.A. in normotensives and untreated hypertensives were normally distributed with slight skewness to the right. The mean P.R.A. for untreated hypertensives (0.65 ng. per ml. per hour) was slightly, but not significantly, lower than that of the normotensive reference group (0.78 ng. per ml. per hour). Previously untreated hypertensives who had been off treatment for four weeks had either high or low P.R.A. depending on the previous treatment. No differences in the angiotensin-generation rate were noted as judged from the P.R.A./P.R.C. ratio. No differences in the renin-substrate concentration between the groups were found. The findings suggest that renin changes in essential hypertenion are secondary to pressure changes. Thus, the renin-angiotensin system may not be of primary pathogenetic importance in the development of essential hypertension. 11128-99-7 (Angiotensin II); EC 3.4.23.15 (Renin); Bengtsson U, Ahlstedt S, Aurell M, Kaijser B. Antazoline-induced immune hemolytic anemia, hemoglobinuria, and acute renal failure. Acta Med Scand 1975; 198(3):223-7. A case of repeated antazoline-induced immune hemolytic anemia, thrombocytopenia, hemoglobinuria, and acute renal failure is reported. The first episode of renal failure occurred after an i.v. pyelography causing an anaphylactic shock, and the two later episodes were preceded by allergic reaction to drugs. Antazoline was given among other remedies, but this drug was the only one used for treatment on every occasion. The clinical picture and the immunological tests, including an antazoline-dependent Coombs' test, indicate that the blood disorders might have been caused by a type 2 allergic reaction and renal lesion by a type 3 reaction, at least on the second and third occasions. 0 (Hemoglobins); 0 (Imidazoles); 60-27-5 (Creatinine); 9007-36-7 (Complement); 91-75-8 (Antazoline); Berglund G, Tibblin G, Aurell M. Urinary noradrenaline excretion and renal function in normal and hypertensive 50-year-old men. Clin Sci Mol Med 1975; 49(5):485-93. Sympathetic nervous system activity, measured by urinary noradrenaline excretion, was determined in a group of untreated hypertensive subjects (n = 35), a reference group (n = 80) and a normotensive group (n = 51), all derived from a random population sample of 50-year-old men. It was compared with casual and resting blood pressure, urinary sodium excretion, urinary cretinine concentration and glomerular filtration rate. Hypertension was defined as systolic pressure greater than 175 or diastolic greater than 115 mmHg on two separate occasions. Normotension was defined as systolic pressure less than 160 and diastolic pressure less than 95 mmHg. 2. There was no difference in the average excretion of noradrenaline during the day or night between the reference, normotensive and hypertensive groups. None of the hypertensive patients had values for urinary noradrenaline excretion during the day above the range found in normotensive subjects, indicating that hypertension with increased sympathetic nervous system activity is uncommon when hypertension in defined as above. 3. No correlation between urinary noradrenaline excretion during the day and blood pressure was found in the reference group or in the normotensive group. In the hypertensive group, there was a negative correlation between urinary noradrenaline excretion and blood pressure after rest. This finding might indicate that factors other than sympathetic nervous system activity determine the level of blood pressure in hypertensive subjects. 4. In the hypertensive group, urinary noradrenaline excretion during the day was positively correlated with both urinary sidium excretion during the day and glomerular filtration rate. Urinary noradrenaline excretion per 24 h was positively correlated with urinary sodium excretion during the same time. High resting blood pressure, low urinary sodium excretion, low glomerular filtration rate and a reversed diurnal rhythm of urinary excretion characterized hypertensive patients with low urinary noradrenaline excretion, indicating more severe hypertension in these hypertensive patients with reduced sympathetic nervous system activity. 51-41-2 (Norepinephrine); 60-27-5 (Creatinine); 7440-23-5 (Sodium); Ewald J, Aurell M. Renal function studies after donor nephrectomy. Scand J Urol Nephrol 1975; 29 Suppl:121-4. The remaining kidney undergoes compensatory hypertrophy after donor nephrectomy. Studies have shown that immediate increases of renal plasma flow (RPF) and glomerular filtration rate (GFR) take place. No studies of tubular functions in kidney donors have previously been published. Nine elderly kidney donors with a mean age of 55 years (range 48-71 years) underwent the following studies before and 6 and 12 months after nephrectomy: GFR, RPF, maximal tubular secretion of para-aminohippurate (TmPAH), net acid excretion after 3 days of ammonium chloride loading and test of the urinary concentration ability. RPFP and GFR decreased postoperatively to a mean of 61 and 63.5 per cent respectively, with a rise of the filtration fraction (FF). TmPAH decreased considerably less, to 76 per cent 6 months postoperatively and 86 per cent 12 months postoperatively. The TmPAH/GFR ratio changed from 0.77 to 0.95 and 0.99 postoperatively. The excretion of acid was slightly reduced concerning the NH4+-excretion but the values for H+-excretion and urinary pH were unchanged. The remaining kidney after donor nephrectomy shows the well-known increases in RPF and GFR. Energy-dependent proximal tubular functions such as TmPAH increase even more, indicating an altered glomerulotubular balance. Distal tubular function such as acidification and urinary concentration ability are essentially unchanged. 0 (Aminohippuric Acids); Wilhelmsen L, Tibblin G, Aurell M, Bjure J, Ekstrom-Jodal B, Grimby G. Ventilatory function and work performance in a representative sample of 803 men age 54 years. Chest 1974; 66(5):506-10. Cough/epidemiology; Dyspnea/epidemiology; Exertion; Heart/radiography; Human; Lung/physiology; Male; Middle Age; Prospective Studies; Questionnaires; Smoking/adverse effects; Spirometry; Sputum/secretion; Aurell M, Jonsson S, Vikgren P. Studies on arterial and renal venous plasma renin activity in hypertensive patients. Acta Med Scand 1973; 193(5):399-406. 0 (Antihypertensive Agents); 11128-99-7 (Angiotensin II); EC 3.4.23.15 (Renin); Aurell M, Berglund G, Jonsson S. Radiorenografi vid hypertoni. Lakartidningen 1972; 69(8):872-8. English title: "Radiorenography in hypertension" Adolescence; Adult; Aged; Angiography; Diagnosis, Differential; Female; Human; Hypertension/diagnosis; Hypertension, Renal/diagnosis/etiology; Kidney Diseases/complications; Kidney Function Tests; Male; Middle Age; Radioisotope Renography; Renal Artery Obstruction/complications/surgery; Claes G, Aurell M, Blohme I, Pettersson S. Experimental and clinical results of continuous hypothermic albumin perfusion. Proc Eur Dial Transplant Assoc 1972; 9:484-90. 0 (Serum Albumin); 60-27-5 (Creatinine); Giese J, Aurell M, Munck O. Peripheral and renal venous plasma renin concentration in hypertensive patients with unilateral renal or renovascular disease. Scand J Urol Nephrol 1972; 6:Suppl 15:39-47. 54-31-9 (Furosemide); EC 3.4.23.15 (Renin); Grimby G, Bjure J, Aurell M, Ekstrom-Jodal B, Tibblin G, Wilhelmsen L. Work capacity and physiologic responses to work. Men born in 1913. Am J Cardiol 1972; 30(1):37-42. Blood Pressure; Coronary Disease; Exercise Test; Exertion; Heart Rate; Hemodynamics; Human; Male; Middle Age; Oxygen Consumption; Prospective Studies; Respiration; Sweden; Aurell M. Klinisk bedomning av njurfunktion med radioaktiva isotoper. Lakartidningen 1971; 68(25):2921-9. English title: "Clinical assessment of renal function with radioactive isotopes" 0 (Chromium Isotopes); 0 (Iodine Isotopes); 7440-63-3 (Xenon); Aurell M, Hansson G, Jagenburg R, Nilsson O. Hyperparathyroidism and maximal glucose reabsorption. Acta Med Scand 1971; 190(5):445-9. 0 (Blood Proteins); 50-99-7 (Glucose); 7440-70-2 (Calcium); 9005-80-5 (Inulin); Aurell M, Jonsson S. Renografi--eu underskattad metod for kvantitativ njurtunktions bedomning. Nord Med 1971; 85(22):703. English title: "Renography--an underestimated method for quantative kidney function assessment?" 11061-68-0 (Insulin); Aurell M, Jonsson S, Nilsson S. On the quantitation of radiorenograms. Scand J Clin Lab Invest 1971; 28(3):291-7. 0 (Aminohippuric Acids); 0 (Iodine Isotopes); 9005-80-5 (Inulin); Aurell M, Vikgren P. Plasma renin activity in supine muscular exercise. J Appl Physiol 1971; 31(6):839-41. 58-93-5 (Hydrochlorothiazide); 7647-14-5 (Sodium Chloride); EC 3.4.23.15 (Renin); Wilhelmsen L, Tibblin G, Aurell M, Bjure J, Ekstrom-Jodal B, Grimby G. Ventilatory capacity and work performance in a random sample of 803 fiftyfour year old men. Scand J Respir Dis Suppl 1971; 77:135. Disability Evaluation; Exercise Test; Exertion; Human; Male; Middle Age; Oxygen Consumption; Physical Fitness; Pulmonary Ventilation; Respiration; Spirometry; Grimby G, Wilhelmsen L, Ekstrom-Jodal B, Aurell M, Bjure J, Tibblin G. Aerobic power and related factors in a population study of men aged 54. Scand J Clin Lab Invest 1970; 26(3):287-94. Body Weight; Exertion; Heart Rate; Human; Male; Middle Age; Oxygen Consumption; Respiration; Aurell M. Renal response in man to plasma volume expansion and angiotensin. Scand J Clin Lab Invest Suppl 1969; 112:1-59. 0 (Aminohippuric Acids); 0 (Plasma Substitutes); 0 (Serum Albumin); 11128-99-7 (Angiotensin II); 7440-09-7 (Potassium); 7440-23-5 (Sodium); 9004-54-0 (Dextrans); Aurell M. Renal clearance of 51Cr-EDTA-complex. Strahlentherapie [Sonderb] 1968; 67:420-4. 0 (Chromium Isotopes); 60-00-4 (Edetic Acid); 9005-80-5 (Inulin); Fritjofsson A, Aurell M. Bilateral renal clearance. Technical problems and the effect of ureteric catheterization on renal function. Scand J Urol Nephrol 1968; 2(2):103-8. Chronic Disease; Female; Human; Hydronephrosis/physiopathology; Kidney/abnormalities/injuries/metabolism/physiopathology; Kidney Diseases/physiopathology; Kidney Function Tests; Kidney Neoplasms/physiopathology; Male; Pyelonephritis/physiopathology; Retroperitoneal Fibrosis/physiopathology; Testicular Neoplasms/physiopathology; Tuberculosis, Renal/physiopathology; Tuberculosis, Urogenital/physiopathology; Urinary Catheterization; Ahlborg B, Ahlborg G, Aurell M, Linroth K. Capacity for brief exercise in relation to capacity for prolonged exercise in man. Acta Med Scand Suppl 1967; 472:182-93. Adolescence; Exertion/physiology; Human; Male; Pulse/physiology; Work; Aurell M, Carlsson M, Grimby G, Hood B. Plasma concentration and urinary excretion of certain electrolytes during supine work. J Appl Physiol 1967; 22(4):633-8. 0 (Phosphates); 7440-09-7 (Potassium); 7440-23-5 (Sodium); Aurell M, Cramer K. Serum lipids and lipoproteins in human pregnancy. Clin Chim Acta 1966; 13(3):278-84. 0 (Glycerides); 0 (Lipids); 0 (Lipoproteins); 0 (Phospholipids); 57-88-5 (Cholesterol); Aurell M, Cramer K, Rybo G. Serum lipids and lipoproteins during long-term administration of an oral contraceptive. Lancet 1966; 1(7432):291-3. 0 (Contraceptives, Oral); 0 (Glycerides); 0 (Lipids); 0 (Lipoproteins); 0 (Phospholipids); 57-63-6 (Ethinyl Estradiol); 57-88-5 (Cholesterol); 68-22-4 (Norethindrone); 7727-37-9 (Nitrogen); Aurell M, Fritjofsson A, Grimby G. Renal extraction of para-aminohippurate during variations in renal blood flow and tubular load in man. Clin Sci 1966; 31(3):461-71. |
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2002-05-26/ B. Haraldsson |