DEFECTIVE RENAL CALCIUM REABSORPTION IN GENETIC HYPERCALCIURIC RATS

Idiopathic hypercalciuria is a frequent cause of calcium (Ca) containi ng kidney stones. We have previously shown that there is increased int estinal Ca absorption in selectively inbred genetic hypercalciuric sto ne forming (GHS) rats; however, excess Ca excretion persists when the rats are fed a low Ca diet indicating a defect in renal Ca reabsorptio n and/or increased bone resorption. To determine if GHS rats have a de fect in renal Ca reabsorption we performed C-14-inulin clearance studi es on parathyroidectomized female GHS and control (Ctl) rats. After th ree baseline collections, chlorothiazide (CTZ) or furosemide (FUR) was infused and three more collections were obtained. Both GFR and filter ed load of Ca did nor differ among the groups; however, fractional and absolute excretion (UCaV) of Ca was three times higher in CHS rats. T he increased Ca excretion was not diminished by a low Ca diet. Urine f low rate nearly tripled in all rats after either FUR or CTZ. After CTZ , UCaV was decreased to a greater extent in GHS compared to Ctl rats. After FUR, U,V was increased to a greater extent in Ctl rats compared to GHS rats. These data indicate that GHS rats have a defect in renal Ca reabsorption, in addition to increased intestinal Ca absorption. Th e effect of CTZ was greater, and that of FUR was smaller, in GHS compa red with CPI rats, suggesting that the defect in renal Ca handling mig ht be al the level of the thick ascending limb.