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Phosphorus Restriction Prevents Rapamycin-Induced Kidney Damage in Rats.

Ana I Raya1,2, Angela Vidal1,2, Ignacio López1,2

  • 1Department of Animal Medicine and Surgery, University of Cordoba, Campus Universitario Rabanales, Cordoba, Spain.

American Journal of Nephrology
|October 9, 2024
PubMed
Summary
This summary is machine-generated.

Rapamycin worsens kidney injury, particularly in rats with reduced renal function, by increasing phosphaturia. Dietary phosphorus restriction effectively prevents rapamycin-induced kidney damage.

Keywords:
KidneyPhosphateRapamycinRat

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Area of Science:

  • Nephrology
  • Pharmacology
  • Toxicology

Background:

  • Conflicting reports exist regarding rapamycin's impact on kidney health.
  • Rapamycin is known to induce phosphaturia, a potential contributor to renal injury.

Purpose of the Study:

  • To investigate the effects of rapamycin on kidney pathology in rats with normal and reduced renal mass.
  • To determine the influence of dietary phosphorus intake on rapamycin-induced nephrotoxicity.

Main Methods:

  • Histopathological examination of rat kidneys following rapamycin treatment (1.3 mg/kg for 22 days) or placebo.
  • Evaluation in rats with normal (control) and reduced (Nx) renal mass.
  • Assessment across varying dietary phosphorus levels: 0.6% (NP), 1.2% (HP), and 0.2% (LP).
  • Quantitative scoring of interstitial nephritis (IN), tubular damage (TD), and nephrocalcinosis (NC).

Main Results:

  • Rapamycin significantly increased IN and TD in Nx rats compared to placebo.
  • Rapamycin elevated NC in both control and Nx rats.
  • High phosphorus (HP) intake exacerbated rapamycin-induced kidney lesions (IN, TD, NC), while low phosphorus (LP) intake prevented them.
  • Rapamycin increased fractional excretion of phosphorus (FEP), correlating strongly with renal lesion scores.

Conclusions:

  • Rapamycin exerts detrimental effects on kidney pathology, primarily affecting tubular and tubulointerstitial structures.
  • Rapamycin-induced nephrotoxicity is more pronounced in rats with pre-existing renal dysfunction and is linked to its phosphaturic effect.
  • Dietary phosphorus restriction is a viable strategy to prevent kidney damage in rats treated with rapamycin.