Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3

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Abstract
Objective:  Although hypercalciuria, a well‐established adverse effect of vitamin D3, 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]2 D3).Methods:  Control rats (C‐C), calcitriol‐treated rats (C‐V; three treatments of 0.5 µg of calcitriol per week) and acid‐ingested (water containing 0.21 mol/L NH4Cl), calcitriol‐treated (three treatments of 0.5 µg 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 NH4Cl, 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.