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The Renin-Angiotensin System Involvement in Cisplatin-Induced Nephrotoxicity: An Overview of Physiological and

Aryan Vakilian1, Sina Mohammadi1, Fatemeh Shokri1

  • 1Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

International Journal of Nephrology
|May 27, 2024
PubMed

Insights

The renin-angiotensin system (RAS) is involved in cisplatin (CDDP) induced kidney damage. RAS interventions show potential for mitigating CDDP nephrotoxicity, with notable gender differences observed.

Area of Science:

  • Nephrology
  • Pharmacology
  • Cardiovascular Physiology

Background:

  • Cisplatin (CDDP) is a vital chemotherapy agent, but its use is limited by significant nephrotoxicity.
  • The renin-angiotensin system (RAS) is implicated in drug-induced kidney damage.

Purpose of the Study:

  • To systematically review the literature linking CDDP-induced nephrotoxicity with the RAS pathway.
  • To explore the physiological and pathological roles of RAS in CDDP nephrotoxicity models.

Main Methods:

  • Systematic review of studies published up to October 2023.
  • Searches conducted in PubMed, Scopus, and Web of Science databases using relevant keywords.
  • Inclusion/exclusion criteria applied to select nine relevant studies.

Main Results:

  • Evidence supports RAS involvement in CDDP nephrotoxicity, alongside inflammation and oxidative stress.
  • RAS-related factors like hOCT2, OATP1B1/1B3, kallikrein-kinin system, and bradykinin receptors are implicated.
  • Angiotensin II worsens CDDP renal damage; RAS inhibition benefits males, while vasodepressor arm activation harms females.

Conclusions:

  • Both classic and nonclassic RAS axes significantly influence CDDP nephrotoxicity.
  • Gender-specific responses to RAS interventions highlight differences in renal function and drug effects.
  • Findings offer insights into RAS-related interventions for managing CDDP nephrotoxicity.

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