Abstract
The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n=8; dosage 30 mg/day) or placebo (n=7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q1/Q3 in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90),P<0.02; 12 months 39 (15/79),P<0.05. GFR was significantly decreased by nifedipine treatment (baseline 157±15, 6 months 122±8, 12 months 111±47 ml/min;P<0.05, mean ± SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121±7, 12 months 124±2 mmHg, mean ± SEM) or diastolic (baseline 72±2, 12 months 74±3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure. The data, however, do not present a recommendation for the general use of nifedipine in these patients as the exact intrarenal mechanism of calcium channel blockers in humans remains to be established.
Similar content being viewed by others
References
Mogensen CE, Christensen CK, Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93, 1984
Viberti GC, Jarrett RJ, Mahmud U, Hill RD, Argryropoulos A, Keen H, Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1:1430–1432, 1982
Mogensen CE, Management of diabetic renal involvement and disease. Lancet 1:867–870, 1988
Parving HH, Smidt UM, Andersen AR, Svendsen PA, Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1:1175–1178, 1983
Parving HH, Hommel E, Prognosis in diabetic nephropathy. Br Med J 299:230–233, 1989
Zatz R, Dunn BR, Meyer TW, Anderson A, Rennke HG, Brenner BM, Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 77:1925–1930, 1986
Marre M, Leblanc HS, Guyenne TT, Menard J, Passa P, Converting enzyme inhibition and kidney function in normotensive diabetic patients with persistent microalbuminuria. Br Med J 294:1448–1452, 1987
Mathiesen ER, Hommel E, Giese J, Parving HH, Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. Br Med J 303:81–87, 1991
Rudberg S, Aperia A, Freyschuss U, Persson B, Enalapril reduces microalbuminuria in young normotensive type 1 (insulin dependent) diabetic patients irrespective of its hypertensive effect. Diabetologia 33:470–476, 1990
Wiegmann TH, Gish Herron K, Chondo AM, L McDougall M, Moore WV, Effect of angiotensin-converting enzyme inhibition of renal function and albuminuria in normotensive type 1 diabetic patients. Diabetes 41:62–67, 1992
Christensen CK, Mogensen CE, Effect of antihypertensive treatment progression of incipient diabetic nephropathy. Hypertension 11:109–113, 1985
Mimram A, Insua A, Ribstein J, Bringer J, Monnier L, Comparative effect of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy. Diabetes Care 11:850–853, 1988
Baba T, Murabayashi S, Takebe K, Comparison of the renal effects of angiotensin converting enzyme inhibitor and calcium antagonist in hypertensive type 2 (non-insulin dependent) diabetic patients with microalbuminuria: a randomized control trial. Diabetologia 32:40–44, 1989
Brochner-Mortensen J, A simple method for determination of glomerular filtration rate. Scand J Clin Lab Invest 30:35–45, 1972
Brochner-Mortensen J, Rodbro P, Selection of routine method for determination of glomerular filtration rate in adult patients. Scand J Clin Lab Invest 36:35–45, 1976
Ram MD, Evans K, Chisholm GD, Measurements of effective renal plasma-flow by the clearance of125I-hippuran. Lancet 2:645–646, 1967
Pedersen MM, Mogensen CE, Jorgensen FS et al, Renal effects from limitation of high dietary protein in normoalbuminuric insulin-dependent diabetic patients. Kidney Int (Suppl) 27:115–121, 1989
Cohen DL, Dodds R, Viberti GC, Effect of protein restriction in insulin dependent diabetics at risk of nephropathy. Br Med J 294:795–798, 1987
Feldt-Rasmussen B, Mathiesen E, Deckert T, Effect of two years of strict metabolic control on the progression of incipient nephropathy in insulin-dependent diabetes. Lancet 2:1300–1304, 1986
Mathiesen ER, Oxenboll B, Johansen K, Svendsen PA, Deckert T, Incipient nephropathy in type 1 (insulin dependent) diabetes. Diabetologia 26:406–410, 1984
Chan JCN, Cockram CS, Nicholls MG, Cheung CK, Swaminathan R, Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis. Br Med J 305:981–985, 1992
Bretzel RG, Bollen CC, Maeser E, Federlin KF, Nephroprotective effects of nitrendipine in hypertensive type I and type II diabetic patients. Am J Kidney Dis 21 (Suppl 3):53–64, 1993
Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M, Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 118:577–581, 1993
Drummond K, Levy-Marchal C, Laborde K et al, Enalapril does not alter renal function in normotensive, normo-albuminuric, hyperfiltering type 1 (insulin-dependent) diabetic children. Diabetologia 32:255–260, 1989
Pedersen MM, Schmitz A, Pedersen EB et al, Acute and long term renal effects of angiotensin converting enzyme-inhibition in normotensive, normoalbuminuric insulin-dependent diabetic patients. Diabetic Med 5:562–569, 1988
Melbourne Diabetic Nephropathy Study Group, Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Br Med J 302:210–216, 1991
Stornello M, Valvo EV, Scarpellato L, Hemodynamic, renal, and humoral effects of the calcium entry blocker nicardipine and converting enzyme inhibitor captopril in hypertensive type 2 diabetic patients with nephropathy. J Cardiovasc Pharmacol 14:851–855, 1989
Bakris GL, Effects of diltiazem or lisinopril on massive proteinuria associated with diabetes mellitus. Ann Intern Med 112:707–708, 1990
Loutzenhiser R, Epstein M, Renal microvascular actions of calcium antagonists. J Am Soc Nephrol 1:3–12, 1990
Anderson S, Rencke HG, Zoyas MA, Brenner BM, Chronic calcium channel blockade fails to lower glomerular pressure and albuminuria in diabetic rats. Clin Res 39:247A, 1991
Mogensen CE, Christensen CK, Vittinghus E, The stages of diabetic renal disease with emphasis on the stage of incipient nephropathy. Diabetes 32 (Suppl 2):64–78, 1983
Hostetter TH, Rennke HG, Brenner BM, The case of intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med 72:375–380, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schnack, C., Capek, M., Banyai, M. et al. Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria. Acta Diabetol 31, 14–18 (1994). https://doi.org/10.1007/BF00580754
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00580754