Influence of Nifedipine on Stone Formation and Renal Function in Cholesterol-Induced Nephrolithiasis in Rats

Abstract

Previous investigations showed that nifedipine limited calcium phosphate stone formation induced by a high-cholesterol diet in rats. This study was performed to obtain further insights into the effects of nifedipine on stone prevention, renal function and urine composition. Male Wistar rats were assigned to one of the following groups: (1) cholesterol diet (n = 22), (2) cholesterol diet plus nifedipine (n = 22) and (3) control (n = 6). A high-cholesterol diet was given for 4 weeks, nifedipine was administered by gavage to group 2 for 4 weeks (50 mg/kg/24 h). During weeks 1 and 4, 5 rats of each group were housed in metabolic cages for urine collection. Sodium (Na), calcium (Ca), magnesium (Mg), phosphate (P(i)), citrate and creatinine were determined in the urine. The kidneys of 4 animals of group 1 and 2 were perfused and removed for histology after 1, 2, 3 and 4 weeks, respectively. Clearance studies (inulin, Na, Ca, Mg, P(i)) were performed (n = 6/group) after 4 weeks. The cholesterol diet induced a marked renal stone formation which was significantly limited by nifedipine [calcification index (week 4) 1.75 +/- 0.5 vs. 0.75 +/- 0.5]. The sequential histological examinations showed that concrement formation started intracellularly after only 1 week in group 1, whereas in group 2 the first concretions were observed only after 3 weeks. The cholesterol diet induced an increased excretion of Ca and P(i) citrate and Mg were reduced. The concomitant application of nifedipine resulted in a higher excretion of Ca, Mg and citrate when compared to the cholesterol group. The inulin clearance was decreased in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)