Endocrine Abstracts

Over 60 generations we have inbred a strain of rats to maximize urine calcium excretion, the most common metabolic abnormality in human stone formers. The rats now excrete 8 - 10 times as much calcium as controls and uniformly form kidney stones. They have been termed genetic hypercalciuric stone forming (GHS) rats. The GHS rats exhibit metabolic abnormalities similar to patients with idiopathic hypercalciuria in that they absorb excessive amounts of intestinal calcium, they fail to adequately reabsorb filtered calcium and bone resorption is uniquely sensitive to 1,25(OH)2D3, all apparently due to an increase in the number of receptors for vitamin D. The GHS rats spontaneously form calcium phosphate stones unless their diet is augmented with an oxalate precursor hydroxyproline. Both the hypercalciuric rat and man appear to be predisposed to initially form calcium phosphate stones and not the more commonly observed calcium oxalate stones. In both the rat and man the upper limit of metastability, that level of supersaturation at which a solid phase forms, increases with increasing calcium oxalate, but not calcium phosphate, supersaturation. Thus rat and man appear protected against calcium oxalate stone formation unless a nucleation site, such as the more easily formed calcium phosphate crystal, is present. Through understanding the mechanisms leading to hypercalciuria and stone formation in the GHS rat we are able to understand stone formation in man and develop effective treatment strategies.