Nephrology Dialysis Transplantation, Vol 13, Issue 3 646-650, Copyright © 1998 by Oxford University Press
H Kloke, J Wetzels, R Koene and F Huysmans
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 proteinuria 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 0.98±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 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.
Key words: blood pressure; nifedipine; orthostasis;
proteinuria; renal disease; selectivity
ORIGINAL ARTICLES
Effects of low-dose nifedipine on urinary protein excretion rate in patients with renal disease
Department of Medicine, Division of Nephrology, University Hospital, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands; Corresponding author
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