Genetic hypercalciuric stone-forming rats

Curr Opin Nephrol Hypertens. 2006 Jul;15(4):403-18. doi: 10.1097/01.mnh.0000232881.35469.a9.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adsorption / drug effects
  • Animals
  • Calcium Oxalate / urine*
  • Calcium, Dietary / administration & dosage
  • Calcium, Dietary / metabolism*
  • Disease Models, Animal*
  • Humans
  • Kidney / metabolism*
  • Kidney Calculi / genetics
  • Kidney Calculi / urine*
  • Rats
  • Rats, Mutant Strains*
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Vitamin D / analogs & derivatives
  • Vitamin D / pharmacology

Substances

  • Calcium, Dietary
  • Receptors, Calcitriol
  • dihydroxy-vitamin D3
  • Vitamin D
  • Calcium Oxalate