Effects of low-dose nifedipine on urinary protein excretion rate in patients with renal disease

Background. The observation that proteinuria is an important determinant of the progression of renal disease has prompted numerous studies on the effects of antihypertensive agents on protein excretion. Reports on the proteinuric effects of calcium-channel blockers are quite controversial. It has been suggested that the short-acting dihydropyridine calcium-channel blocker nifedipine increases protein excretion by interference with tubular protein reabsorption. Methods. In a randomized controlled trial 10 patients with renal disease and proteinuria were treated 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 investigated during a clearance study in the supine position after the first dose. After 1 week of treatment urinary protein excretion rates were measured in 24-h urine samples collected in the ambulatory patient in consecutive fractions of 4-8 h during normal daily activities. Results. After the first dose nifedipine lowered mean arterial blood pressure in the supine position by 7+/-1 mmHg (<0.01), attenuated proximal tubular sodium reabsorption (fractional excretion of sodium 3.48+/-0.49 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 decrease in blood pressure was not accompanied by decreases in urinary albumin or IgG excretion rates. The selectivity index as well as GFR, RPF, and FF did not change. Continued treatment for 1 week with nifedipine did not influence 24-h protein excretion. However, we observed a rise 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 proteinuria. During nifedipine the increase in proteinuria was more marked and correlated with the selectivity index. Conclusions. (1) Nifedipine 10 mg orally did not impair tubular protein reabsorption. (2) Nifedipine had no immediate antiproteinuric effect despite the observed blood pressure reduction. (3) Nifedipine increased proteinuria in ambulatory urine collections. This latter observation might explain the seemingly different effects of dihydropyridine calcium-channel blockers as reported in previous studies.