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Related Experiment Videos

Chronic cisplatin nephropathy in rats

G Brillet1, G Deray, M Dubois

  • 1Department of Nephrology, Hôpital Pitie, Paris, France.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|January 1, 1993
PubMed
Summary

Repeated cisplatin doses cause chronic kidney damage, reducing glomerular filtration rate (GFR). This kidney toxicity is dose-dependent and persists long-term, with cumulative effects observed in rats.

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Area of Science:

  • Nephrology
  • Toxicology
  • Pharmacology

Background:

  • Long-term renal effects of cisplatin are poorly understood.
  • Cisplatin is a widely used chemotherapy agent with known nephrotoxic potential.

Purpose of the Study:

  • To investigate the chronic renal effects of various cisplatin dosing regimens in Sprague-Dawley rats.
  • To evaluate the dose-dependency and temporal stability of cisplatin-induced nephropathy.

Main Methods:

  • Male Sprague-Dawley rats received different cisplatin doses and schedules (Group I: 2x5mg/kg, Group II: 4x2.5mg/kg, Group III: 1x5mg/kg + 4x2.5mg/kg).
  • Renal function was assessed 1, 3, and 6 months post-treatment via [99mTc]DTPA and creatinine clearance.
  • Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion and kidney histology were analyzed.

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Main Results:

  • Cisplatin significantly decreased glomerular filtration rate (GFR) and creatinine clearance in all treated groups.
  • Group III showed significantly lower GFR at 3 months compared to Groups I and II.
  • Histological analysis revealed tubulointerstitial damage, including atrophy, dilatation, mononuclear cell infiltration, and cyst formation, which were more severe in Group III.

Conclusions:

  • Repeated cisplatin administration induces chronic tubulointerstitial nephropathy with sustained GFR reduction.
  • Cisplatin nephrotoxicity is dose-related and its severity is not mitigated by dose fractionation.
  • The observed renal lesions and functional deficits are stable over the 6-month evaluation period.