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

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 mg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 mg 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.

Increased biological response to 1,25(OH)2D3in genetic hypercalciuric stone-forming rats

“…Whether 1,25D treatment leads to reduced proximal tubule citrate reabsorption is not known. Okamoto et al (77) found a trend to higher U citrate in male Wister rats treated with 1,25D. While studies in humans demonstrated a link between VDR polymorphisms and tubular reabsorption of citrate (62, 73), we are not aware of any studies directly linking 1,25D levels and citrate excretion.…”

Effect of ammonium chloride supplementation on urine pH and urinary fractional excretion of electrolytes in goats

“…However, inconsistent results have been reported. 25 To our knowledge, no studies have examined urinary FE of electrolytes in goats fed grass hay with or without supplemental ammonium chloride. 18 Also, changes in bone morphology and subsequent osteopenia associated with dietary-induced metabolic acidosis in sheep have been reported.…”

Vitamin D repletion does not alter urinary calcium excretion in healthy postmenopausal women

“…One study suggested that a high‐protein, high‐sodium diet in postmenopausal women, considered typical for many women in the USA, detrimentally affects calcium and bone metabolism in those with a certain vitamin D‐receptor genotype [15]. A recent study in rats showed that hypercalciuria occurred with vitamin D treatment only when they were fed a chronic high dietary acid load, suggesting that vitamin D treatment, even in high dosages, does not lead to hypercalciuria unless other dietary risk factors are present [16]. Given these data, we theorise that the risk of hypercalciuria from vitamin D supplementation, using accepted blood measures of vitamin D adequacy as outcome variables, might be smaller than the risks from innumerable different combinations of genetic and dietary alterations that could contribute to altered calcium transport in the intestine, kidney and bone [17].…”