Cyclophosphamide-Induced Nephrotoxicity and Nephroprotection in Rodent Models: A Systematic Review and Random-Effects Meta-Analysis (2010–2025)

TL;DR

This study reviews rodent models to understand how cyclophosphamide causes kidney damage and how to protect against it.

Contribution

The paper introduces a systematic review and meta-analysis of CP nephrotoxicity and nephroprotection in rodent models from 2010–2025.

Findings

Cyclophosphamide significantly increases serum creatinine and urea levels in rodents.

Nephroprotective interventions show consistent effects on oxidative stress markers but less on functional recovery.

Reporting inconsistencies limit the ability to rank protective agents reliably.

Abstract

Cyclophosphamide (CP) is extensively used in oncology and as an immunosuppressant, but dose-limiting renal injury remains a major constraint. We systematically reviewed in vivo rodent models of CP nephrotoxicity (2010–2025) and meta-analysed core outcomes while separating the model effect (CP vs. control) from the treatment effect (intervention + CP vs. CP-only). Fifty-four studies met eligibility criteria, and random-effects syntheses were feasible for serum creatinine, serum urea, and renal oxidative stress markers. CP produced a marked functional deterioration, increasing serum creatinine by 1.059 mg/dL (95% CI 0.517–1.601; k = 9) and serum urea by 39.852 mg/dL (95% CI 6.557–73.148; k = 9). Across intervention studies, protective effects were most consistently expressed in oxidative endpoints (MDA/TBARS reduction and glutathione preservation), whereas functional recovery estimates were more variable and frequently limited by incomplete reporting and between-study heterogeneity. Overall, the evidence base supports CP as a robust preclinical model of combined functional and redox-mediated renal injury and indicates that multiple mechanistic classes of interventions can partially mitigate injury, but current reporting and design heterogeneity preclude reliable ranking of candidate agents. The protocol was registered on OSF.

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