INCREASED URINARY SATURATION AND KIDNEY CALCIUM CONTENT IN GENETIC HYPERCALCIURIC RATS

We have established a colony of genetic hypercalciuric (IH) rats as a model of idiopathic hypercalciuria in humans. To test the hypothesis t hat hypercalciuria can cause crystallization in kidneys through increa sed supersaturation, in the absence of confounding effects of diet and whatever complex inhibitor disorders underlay stone disease, we fed m ales and females of the 21st generation of IH rats 13 g per day of a l ow calcium (LCD, 0,02% Ca), followed by a normal calcium (NCD, 0.6% Ca ) and then a high calcium (HCD, 1.2% Ca) diet, each for seven days. Du ring the last 24 hours of each period complete urine collections were obtained and analyzed for all substances known to affect urinary calci um oxalate (CaOx) and brushite (CaHPO4) supersaturation. Relative supe rsaturation with respect to the solid phases of CaOx and CaHPO4 were t hen calculated. Compared to same gender controls (Ctl) urine calcium e xcretion was higher in the female IH rats on all diets and in the male IH rats on NCD and HCD. The female and male IH rats on NCD and HCD we re supersaturated with respect to CaOx; however, the male and female C tl were supersaturated with respect CaOx only on HCD. The female IH ra ts on NCD and HCD and the male IH rats on NCD were supersaturated with respect to CaHPO4; however, neither the male nor female Ctl rats were supersaturated with respect to CaHPO, on any diet. On NCD and HCD uri ne supersaturation with respect to CaHPO4 by females exceeded that of males. Kidney calcium content was greater in the female IH rat (120 +/ - 13 mug/g kidney) than in any other group (male IH, 68 +/- 6; female Ctl, 74 +/- 4 and male Ctl 62 +/- 4; all P < 0.01 vs. female IH) and c alcium content was correlated with CaHPO4 but not CaOx. Thus, female I H rats have greater urinary CaHPO4 supersaturation than Ctl rats or ma le IH rats, and these female IH rats have a greater kidney calcium con tent. The increased urinary calcium concentration in this inbred strai n of hypercalciuric rats leads to urinary supersaturation, leading to calcium precipitation within the kidney.