Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D sub(3)

Objective:Although hypercalciuria, a well-established adverse effect of vitamin D sub(3), can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1-25[OH] sub(2) D sub(3)). Methods:Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 mu g of calcitriol per week) and acid-ingested (water containing 0.21 mol-L NH sub(4)Cl), calcitriol-treated (three treatments of 0.5 mu g of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. Results:The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)-creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. Conclusions:The ingestion of NH sub(4)Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol.