Proton pump inhibitors in prevention of cisplatin-induced nephrotoxicity: a systematic review.
Sina Pakkhesal, Pouya Mohammadi, Afra Rezagholizadeh et al.
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In 30 seconds
This systematic review assessed whether proton pump inhibitor (PPI) co-administration prevents cisplatin-related kidney injury and whether it is safe. It included eight studies involving 1062 participants: two randomised trials and six non-randomised studies. Findings conflicted: two retrospective cohorts suggested protection, while one prospective cohort associated PPI use with increased acute kidney injury risk (OR 2.78; p = 0.010). A trial reported nephrotoxicity in 0% with high-dose pantoprazole versus 25% in controls, but this primary-endpoint difference was not statistically significant (p = 0.078). The authors concluded that evidence is insufficient for a clear safety or efficacy conclusion.
Key findings
- Across eight studies (1062 participants), results on PPI use and cisplatin-related renal outcomes were inconsistent.
- One trial reported nephrotoxicity in 0% with high-dose pantoprazole versus 25% in controls (p = 0.078).
- One prospective cohort identified PPI use as an independent AKI risk factor (OR 2.78; p = 0.010) and reported worse post-treatment eGFR outcomes.
- Four studies found no statistically significant association between PPI use and renal outcomes.
Why it matters
PPIs have a proposed mechanism for limiting cisplatin uptake into renal tubular cells, but they have also been linked to AKI. The conflicting clinical findings mean that a plausible protective mechanism cannot be assumed to translate into net renal benefit. Clarifying both kidney outcomes and potential harms is important when evaluating PPI co-administration during cisplatin therapy.
What to keep in mind
Clinical, methodological, and statistical heterogeneity was extreme, so the review used narrative synthesis rather than quantitative meta-analysis. The evidence included only two randomised trials.