EFFECTS OF LOW-DOSE NIFEDIPINE ON URINARY PROTEIN EXCRETION RATE IN PATIENTS WITH RENAL-DISEASE

Background. The observation that proteinuria is an important determina nt of the progression of renal disease has prompted numerous studies o n the effects of antihypertensive agents on protein excretion. Reports on the proteinuric effects of calcium-channel blockers are quite cont roversial. It has been suggested that the short-acting dihydropyridine calcium-channel blocker nifedipine increases protein excretion by int erference with tubular protein reabsorption. Methods. In a randomized controlled trial 10 patients with renal disease and proteinuria were t reated with a dose of 10 mg nifedipine o.d. (slow release formulation) for 1 week. The acute effects on renal and systemic haemodynamics and on urinary albumin, IgG, and beta(2)-microglobulin excretion were inv estigated during a clearance study in the supine position after the fi rst dose. After 1 week of treatment urinary protein excretion rates we re measured in 24-h urine samples collected in the ambulatory patient in consecutive fractions of 4-8 h during normal daily activities. Resu lts. After the first dose nifedipine lowered mean arterial blood press ure in the supine position by 7+/-1 mmHg (<0.01), attenuated proximal tubular sodium reabsorption (fractional excretion of sodium 3.48+/-0.4 9 vs 2.62+/-0.35% during control, P<0.02), but did not affect proximal tubular protein reabsorption (fractional urinary excretion of beta(2) -microglobulin 0.97+/-0.30 vs 0.9+/-0.32% during control, NS). The dec rease in blood pressure was not accompanied by decreases in urinary al bumin or IgG excretion rates. The selectivity index as well as GFR, RP F, and FF did not change. Continued treatment for 1 week with nifedipi ne did not influence 24-h protein excretion. However, we observed a ri se of proteinuria during daily activities in the first 4 h after drug intake compared to the start of the study with the patients in supine position. During control measurements there was a slight increase in p roteinuria. During nifedipine the increase in proteinuria was more mar ked and correlated with the selectivity index. Conclusions. (1) Nifedi pine 10 mg orally did not impair tubular protein reabsorption. (2) Nif edipine had no immediate antiproteinuric effect despite the observed b lood pressure reduction. (3) Nifedipine increased proteinuria in ambul atory urine collections. This latter observation might explain the see mingly different effects of dihydropyridine calcium-channel blockers a s reported in previous studies.