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Related Experiment Videos

Stone formation in genetic hypercalciuric rats

D A Bushinsky1, M D Grynpas, E L Nilsson

  • 1Nephrology Unit, University of Rochester, New York, USA.

Kidney International
|December 1, 1995
PubMed
Summary

Genetic hypercalciuric rats developed spontaneous kidney stones due to increased urine calcium excretion. These stones were identified as apatite, marking a breakthrough in nephrolithiasis research.

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Area of Science:

  • Nephrology
  • Urology
  • Animal Models

Background:

  • Genetic hypercalciuric (GH) rats were developed through 29 generations of selective inbreeding to exhibit significantly elevated urine calcium (UCa) excretion compared to control (Ctl) rats.
  • Understanding the impact of sustained high UCa on urinary stone formation is crucial for developing effective prevention and treatment strategies.

Purpose of the Study:

  • To investigate the effects of genetically induced hypercalciuria on urinary supersaturation and the development of kidney stones.
  • To characterize the composition and morphology of stones formed in this novel animal model.

Main Methods:

  • Pair-fed 15 GH and 15 Ctl rats a 1.2% calcium diet for 18 weeks.
  • Monitored urine supersaturation every two weeks and examined urinary tracts for stones every six weeks.

Related Experiment Videos

  • Analyzed formed stones using Scanning Electron Microscopy (SEM), X-ray and electron diffraction, and X-ray microanalysis.

    • Main Results:

    • GH rats exhibited consistently higher UCa levels, leading to increased supersaturation for calcium hydrogen phosphate (CaHPO4) and calcium oxalate (CaOx).
    • A progressive increase in stone incidence was observed in GH rats, with all rats developing stones by 18 weeks; no stones formed in Ctl rats.
    • SEM, diffraction, and microanalysis confirmed the stones were poorly crystalline apatite, not nephrocalcinosis.

    Conclusions:

    • This study establishes the first animal model of spontaneous nephrolithiasis, characterized by apatite stone formation.
    • The elevated CaHPO4 supersaturation in GH rats, relative to CaOx, likely explains the apatite composition of the stones.
    • This GH rat model provides a valuable tool for studying the pathogenesis and potential treatments of kidney stone disease.