Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3.
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 microg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 microg 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.
Okamoto
Naohiko
N
Department of Urology, University of Tokyo, Tokyo, Japan.
Aruga
Seiji
S
Tomita
Kyoichi
K
Takeuchi
Takumi
T
Kitamura
Tadaichi
T
D000643:Ammonium Chloride / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D002130:Calcium Phosphates / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage*; D007669:Kidney Calculi / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014815:Vitamins / Q000008:administration & dosage*
D002130:Calcium Phosphates; D014815:Vitamins; D000643:Ammonium Chloride; D002762:Cholecalciferol; C020243:calcium phosphate; D002117:Calcitriol