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Updated: May 22, 2026

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
08:50

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

Published on: July 3, 2013

Nox2 is a mediator of chronic CsA nephrotoxicity

A Djamali1, S Reese, O Hafez

  • 1Division of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. axd@medicine.wisc.edu

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|May 10, 2012
PubMed

Insights

Nox2, a key enzyme, drives calcineurin inhibitor-induced kidney fibrosis by promoting epithelial to mesenchymal transition. Inhibiting Nox2 may offer a novel strategy to treat chronic nephrotoxicity in transplant patients.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Calcineurin inhibitors (CNIs) like cyclosporine A (CsA) and tacrolimus (TAC) are vital immunosuppressants but can cause chronic kidney disease.
  • The precise molecular mechanisms underlying CNI-induced renal fibrosis remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Nox2, a NADPH oxidase, in CNI-induced renal fibrosis.
  • To explore potential therapeutic strategies targeting Nox2 for CNI nephrotoxicity.

Main Methods:

  • In vitro studies using NRK52E cells treated with CsA and TAC.
  • In vivo studies in Fisher344 rats and Nox2-deficient mice treated with CsA.
  • Analysis of kidney biopsies from human liver transplant recipients.

Main Results:

  • CNIs increased Nox2 expression and epithelial to mesenchymal transition (EMT) markers in vitro.
  • Nox2 upregulation and fibrotic markers were observed in CNI-treated rats and mice.
  • Inhibition of Nox2 reduced fibrogenesis in animal models.
  • Elevated Nox2 and α-SMA levels correlated with CNI nephrotoxicity in human kidney biopsies.

Conclusions:

  • Nox2 plays a critical role in CNI-induced renal fibrosis, likely mediated by TGF-β1 signaling.
  • Targeting Nox2 presents a promising therapeutic avenue for mitigating chronic CNI nephrotoxicity in solid organ transplantation.

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