Laboratory Investigation

Kidney International (1995) 48, 1705–1713; doi:10.1038/ki.1995.468

Stone formation in genetic hypercalciuric rats

David A Bushinsky, Marc D Grynpas, Erica L Nilsson, Yasushi Nakagawa and Fredric L Coe

Nephrology Unit, University of Rochester, Rochester, New York, USA; Pathology Department, University of Toronto, Toronto, Ontario, Canada; and Nephrology Program, University of Chicago, Chicago, Illinois, USA

Correspondence: David A Bushinsky MD, Departments of Medicine and Physiology, Nephrology Unit, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 675, Rochester, New York 14642, USA.

Received 20 April 1995; Revised 23 June 1995; Accepted 26 June 1995.

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Abstract

Stone formation in genetic hypercalciuric rats. Our genetic hypercalciuric (GH) rats have been selected and inbred for 29 generations to maximize urine calcium (UCa) excretion compared to identical gender controls (Ctl). To determine the effect of the increased UCa 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 UCa 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.

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