Summary
The effect of enalapril on albumin excretion rate was studied in two groups of age- and sex-matched Type 1 (insulin-dependent) diabetic patients, aged 15–20 years, with persistent microalbuminuria >20 μg/min. Group 1 contained six patients with systolic blood pressure ≥ 75th percentile for age and sex, group 2 six normotensive patients. Enalapril (10–20 mg/day) was given for six months. Albumin excretion rate, glomerular filtration rate, renal plasma flow, blood pressure at rest and during exercise, and angiotensin converting enzyme activity were measured before, after three weeks' and six months' treatment and six months after treatment withdrawal. Albumin excretion rate decreased in all patients after three weeks' (mean decreases 55% in group 1, 65% in group 2) and six months' treatment (35% in group 1, 61% in group 2). Systolic blood pressure remained unchanged in both groups. Diastolic pressure was reduced after three weeks in group 1 (p=0.001). No reduction in increment in systolic pressure during exercise test occurred in any group during treatment. Angiotensin converting enzyme activity decreased in all patients after three weeks (p=0.001) and six months (p=0.003). This correlated to the decrease in albumin excretion rate after three weeks (r=0.79, p=0.05) and six months (r=0.59, p=0.04). HbA1c, mean blood glucose and glomerular filtration rate remained unchanged during the study in both groups. Renal plasma flow tended to increase after three weeks' and six months' treatment in group 2 (p=0.06, respectively) but not in group 1. Filtration fraction decreased after three weeks (p=0.04) only in group 2. In conclusion, enalapril reduces the albumin excretion rate in adolescent diabetic patients with or without elevated blood pressure. This reduction was not accompanied by a decreased systemic pressure but rather by a fall in filtration fraction in normotensive patients, indicating a direct effect, irrespective of the antihypertensive, on intraglomerular pressure.
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Viberti GC, Hill RD, Jarrett RJ, Argyropaulos A, Mahmud Y, Keen H (1982) Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet I: 1430–1432
Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 89–93
Parving H-H, Hommel E, Mathiesen, Skott P, Edsberg B, Bahnsen M, Lauritzen M, Hougaard P, Lauritzen E (1988) Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin-dependent diabetes. Br Med J 296: 156–160
Mathiesen ER, Oxenboll B, Johansen K, Svendsen PA, Deckert T (1985) Incipient nephropathy in Type 1 (insulin-dependent) diabetes. Diabetologia 26: 406–410
Mogensen CE, Christensen CK (1985) Blood pressure changes and renal function in incipient and overt diabetic nephropathy. Hypertension 7: 64–73
Berglund J, Lins PE, Adamson U, Lins LE (1987) Microalbuminuria in long-term insulin-dependent diabetes mellitus. Prevalence and clinical characteristics in normotensive population. Acta Med Scand 222: 333–338
Christensen CK, Mogensen CE (1985) Effect of antihypertensive treatment on progression of incipient diabetic nephropathy. Hypertension 7: 109–113
Working group of hypertension (1987) Statement on hypertension. Diabetes Care 10: 764–776
Zats R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM (1986) Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 77: 1925–1930
Marre M, Chatellier G, Leblanc H, Guyene TT, Menard J, Passa P (1988) Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. Br Med J 297: 1092–1095
Insua A, Ribstein J, Mimran A (1988) Comparative effect of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy. Postgrad Med J 64 [Suppl 3]: 59–62
Romanelli G, Giustina A, Cimino A, Valentini U, Agabitiosei E, Muiesan G, Giustina G (1989) Short term effect of captopril on microalbuminuria induced by exercise in normotensive diabetics. Br Med J 298: 284–288
Blood Pressure Measurements (1977) Prepared by the National Heart, Lung, and Blood Institute's Task Force on Blood Pressure Control in Children, Vol 59, No 5, part 2
Simsom DC (1988) Insulin sensitivity and the effects of antihypertensive agents: implications for the treatment of hypertension in the patient with diabetes mellitus. Postgrad Med J 64 [Suppl 3]: 39–47
Rudberg S, Dahlquist G, Aperia A, Persson B (1988) Reduction of protein intake decreases glomerular filtration rate in young Type 1 (insulin-dependent) diabetic patients mainly in hyperfiltrating patients. Diabetologia 31: 878–883
Åstrand P-O, Rodahl K (1977) Textbook of Work Physiology. Physiological Bases of Exercise. 2nd edn. Mc Graw-Hill, USA, pp 289–361
Hilger HH, Klumper SD, Ullrich J (1958) Mikroanalytische Untersuchungen über die Wasser- und Natriumrückresorption aus den Sammelrohrenden der Säugetierniere. Pflügers Arch 267: 218–237
Smith HW, Finkelstein N, Aliminosa L, Crawford B, Graber M (1945) The renal clearances of substituted hippuric acid and derivates and other aromatic acids in dog and man. J Clin Invest 24: 388–401
Dalton RN, Wiseman MJ, Turner C, Viberti GC (1988) Measurement of urinary para-aminohippuric acid in glycosuric diabetics. Kidney Int 34: 117–120
Gomeri J (1942) Modification of colorimetric phosphorous determination for the use with photoelectric colorimeter. J Lab Clin Med 27: 955–960
Friedman PJ, Dunn PJ, Jury DR (1986) Metoprolol and albumin excretion in diabetes. Lancet II: 1042–1043
Hommel E, Mathiesen E, Edsberg B, Bahnen M, Parving HH (1986) Acute reduction of arterial blood pressure reduces albumin excretion in Type 1 (insulin-dependent) diabetic patients with incipient nephropathy. Diabetologia 29: 211–215
Taguma Y, Kitamoto Y, Futaki G, Ueda H, Monma H, Ishizaki M, Takahashi, Sekino H, Sasaki Y (1985) Effect of captopril on heavy proteinuria in azotemic diabetics. N Engl J Med 313: 1617–1620
Parving H-H, Hommel E, Damkjaer Nielsen M, Giese J (1989) Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. Br Med J 299: 533–536
Klahr S, Schreiner G, Ichikava I (1988) The progression of renal disease. N Engl J Med 318: 1657–1666
Raij L, Keane WF (1985) Glomerular mesangium: its function and relationship to angiotensin II. Am J Med 79: 24–30
Cooper ME, Allen TJ, Macmillan PA, Clarke BE, Jerums G, Doyle AE (1989) Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat. Diabetologia 32: 326–328
Hollenberg NK, Meggs LG, Williams GH, Katz J, Garnic JD, Harrington DP (1981) Sodium uptake and renal responses to captopril in normal man and in essential hypertension. Kidney Int 20: 240–245
Mau Pedersen M, Schmitz A, Bjerregaard Pedersen E, Danielsen H, Sandhal Christiansen J (1988) Acute and long term renal effects of angiotensin converting enzyme inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients. Diabetic Med 5: 562–569
Kupin WC, Cortes P, Dumler F, Kilates MC, Lewin NW (1987) Effect on renal function of change from high to moderate protein intake in type 1 diabetic patients. Diabetes 36: 73–79
Wiseman MJ, Bognetti E, Dodds R, Keen H, Viberti GC (1987) Changes in renal function in response to protein restricted diet in Type 1 (insulin-dependent) diabetic patients. Diabetologia 30: 154–159
Feldt-Rasmussen B, Mathiesen ER, Deckert T (1986) Effect of two years strict metabolic control on the progression of incipient nephropathy in insulin-dependent diabetes. Lancet II: 1300–1304
Persson B, Thorén C (1980) Prolonged exercise in adolescent boys with juvenile diabetes mellitus. Acta Paediatr Scand [Suppl 283]: 62–69
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Rudberg, S., Aperia, A., Freyschuss, U. et al. Enalapril reduces microalbuminuria in young normotensive Type 1 (insulin-dependent) diabetic patients irrespective of its hypotensive effect. Diabetologia 33, 470–476 (1990). https://doi.org/10.1007/BF00405108
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DOI: https://doi.org/10.1007/BF00405108