INFLUENCE OF NIFEDIPINE ON STONE FORMATION AND RENAL-FUNCTION IN CHOLESTEROL-INDUCED NEPHROLITHIASIS IN RATS

Previous investigations showed that nifedipine limited calcium phospha te stone formation induced by a high-cholesterol diet in rats. This st udy was performed to obtain further insights into the effects of nifed ipine on stone prevention, renal function and urine composition. Male Wistar rats were assigned to one of the following groups: (1) choleste rol diet (n = 22), (2) cholesterol diet plus nifedipine (n = 22) and ( 3) control (n = 6). A high-cholesterol diet was given for 4 weeks, nif edipine 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 metabol ic cages for urine collection. Sodium (Na), calcium (Ca), magnesium (M g), phosphate (P(i)), citrate and creatinine were determined in the ur ine. The kidneys of 4 animals of group 1 and 2 were perfused and remov ed for histology after 1, 2, 3 and 4 weeks, respectively. Clearance st udies (inulin, Na, Ca, Mg, P(i)) were performed (n = 6/group) after 4 weeks. The cholesterol diet induced a marked renal stone formation whi ch was significantly limited by nifedipine [calcification index (week 4) 1.75 +/- 0.5 vs. 0.75 +/- 0.5]. The sequential histological examina tions showed that concrement formation started intracellularly after o nly 1 week in group 1, whereas in group 2 the first concretions were o bserved 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 an d citrate when compared to the cholesterol group. The inulin clearance was decreased in the latter group. Nifedipine limited this decrease. The fractional excretion (FE) of Ca, P(i) and Mg was increased with th e cholesterol diet. Nifedipine further increased the FE of Ca and Mg; FE of P(i) was decreased when compared to group 1. Our results show th at nifedipine limits nephrolithiasis and the deterioration of renal fu nction in rats fed a cholesterol diet. Tubular cells obviously play a key role in the process of cholesterol-induced stone formation, probab ly being more important than changes in urine composition.