title: Modeling hypercalciuria in the genetic hypercalciuric stone-forming rat.
abstract: OBJECTIVE
  In this review, we discuss how the genetic hypercalciuric stone-forming (GHS) rats, which closely model idiopathic hypercalciuria and stone formation in humans, provide insights into the pathophysiology and consequences of clinical hypercalciuria.
  
  
  RESULTS
  Hypercalciuria in the GHS rats is due to a systemic dysregulation of calcium transport, as manifest by increased intestinal calcium absorption, increased bone resorption and decreased renal tubule calcium reabsorption. Increased levels of vitamin D receptor in intestine, bone and kidney appear to mediate these changes. The excess receptors are biologically active and increase tissue sensitivity to exogenous vitamin D. Bones of GHS rats have decreased bone mineral density (BMD) as compared with Sprague-Dawley rats, and exogenous 1,25(OH)2D3 exacerbates the loss of BMD. Thiazide diuretics improve the BMD in GHS rats.
  
  
  CONCLUSIONS
  Studying GHS rats allows direct investigation of the effects of alterations in diet and utilization of pharmacologic therapy on hypercalciuria, urine supersaturation, stone formation and bone quality in ways that are not possible in humans.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Frick
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Krieger
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
mesh_terms: D000818:Animals; D002136:Calcium, Dietary / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D053565:Hypercalciuria / Q000188:drug therapy / Q000378:metabolism*; D007669:Kidney Calculi / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D002136:Calcium, Dietary; D018167:Receptors, Calcitriol