Effect of acidosis on urine supersaturation and stone formation in genetic hypercalciuric stone-forming rats

Background. We have successively inbred over 45 generations a strain of rats to maximize urine calcium excretion. The rats now consistently excrete 8 to 10 times as much calcium as controls and uniformly form poorly crystalline calcium phosphate kidney stones. In humans with calcium nephrolithiasis, consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones; however, the effect of this diet on urinary supersaturation with respect to the common solid phases found in kidney stones has not been determined. Methods. To determine the effect of the addition of an acid precursor on urine ion excretion, supersaturation, and stone formation, we fed these genetic hypercalciuric stone-forming (GHS) rats 13 g/day of a 1.2% calcium diet with 0.0, 0.5, 1.0, or 1.5% NH(4)Cl in the drinking water for 14 weeks (N = 8 for each). Urine was collected and analyzed every two weeks. Results. As expected, the addition of dietary NH(4)Cl led to a progressive fall in urine pH and urine citrate, while urine ammonium increased. Urine calcium and phosphorus increased, while urine oxalate fell. Increasing dietary NH(4)Cl led to a fall in supersaturation with respect to CaHP0(4) (brushite) and CaOx and a rise in supersaturation with respect to uric acid. In spite of differences in supersaturation, most rats in each group formed stones that contained calcium phosphate and not calcium oxalate. Conclusions. Thus, while the provision of additional dietary acids alters urinary ion excretion and lowers supersaturation with respect to CaHP04 and CaOx, it does not change the character or rate of stone formation in the GHS rats.