Genetic hypercalciuric stone-forming rats.
OBJECTIVE
We will describe the pathophysiology of hypercalciuria and the mechanism of the resultant stone formation in a rat model and draw parallels to human hypercalciuria and stone formation.


RESULTS
Through inbreeding we have established a strain of rats that excrete 8-10 times more urinary calcium than control rats. These genetic hypercalciuric rats absorb more dietary calcium at lower 1,25-dihydroxyvitamin D3 levels. Elevated urinary calcium excretion on a low-calcium diet indicated a defect in renal calcium reabsorption and/or an increase in bone resorption. Bone from hypercalciuric rats released more calcium when exposed to 1,25-dihydroxyvitamin D3. Bisphosphonate significantly reduced urinary calcium excretion in rats fed a low-calcium diet. Clearance studies showed a primary defect in renal calcium reabsorption. The intestine, bone and kidneys of the hypercalciuric rats had increased numbers of vitamin D receptors. When hydroxyproline is added to their diet they form calcium oxalate stones, the most common stone type in humans. Increased numbers of vitamin D receptors may cause hypercalciuria in these rats and humans.


CONCLUSIONS
Understanding the mechanism of hypercalciuria and stone formation in this animal model will help clinicians devise effective treatment strategies for preventing recurrent stone formation in humans.
Bushinsky
David A
DA
Division of Nephrology, Department of Medicine, University of Rochester School of Medicine, Rochester, New York 14642, USA. David_Bushinsky@urmc.rochester.edu
Frick
Kevin K
KK
Nehrke
Keith
K
D000327:Adsorption / Q000187:drug effects; D000818:Animals; D002129:Calcium Oxalate / Q000652:urine*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007669:Kidney Calculi / Q000235:genetics / Q000652:urine*; D051381:Rats; D011922:Rats, Mutant Strains; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology
D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002129:Calcium Oxalate