STONE FORMATION IN GENETIC HYPERCALCIURIC RATS

Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (U-Ca) excretion compared to identical gender controls (Ctl). To determine the effect of the increased U-Ca on urinary supersaturation and stone formation, we pair fed 15 GH and 15 Ctl rats a standard 1.2% calcium diet for 18 weeks, measured urine supersaturation every two weeks, and examined the urinary tract of 1/3 of the rats for the presence of stones every six weeks. Any stones formed were studied by SEM, X-ray and electron diffraction and X-ray microanalysis. Over the entire study U-Ca was increased in the GH compared to Ctl, resulting in greater supersaturation with respect to calcium hydrogen phosphate (CaHPO4) at all times and calcium oxalate (CaOx) at most times. There was a progressive increase in the incidence of stone formation in GH rats with one of five rats having stones at six weeks, three of five with stones at 12 weeks and five of five with stones at 18 weeks. There were no stones formed in Ctl rats. SEM reveals discrete stones and not nephrocalcinosis. X-ray and electron diffraction and X-ray microanalysis reveal the stones to be poorly crystalline apatite which is a solid phase of calcium and phosphate. Compared to Ctl, in the GH rats the saturation ratio for CaHPO4 increased proportionally more than that for CaOx, perhaps explaining why the rats formed apatite and not oxalate stones. This is the first description of an animal model of spontaneous nephrolithiasis.