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Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review and Meta-Analysis

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Abstract

Purpose

Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20–40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA.

Methods

We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018, without language restriction. All studies (observational and interventional) assessing a CIA prevention method for adults receiving at least one course of cisplatin were eligible. The primary outcome was acute nephrotoxicity, as defined by the AKI-KDIGO classification (2012). The odds ratio and corresponding 95% confidence interval were used to assess the associations. We used narrative synthesis in case of heterogeneity regarding intervention, population, or outcome. When possible, a random-effects model was used to pool studies. The heterogeneity between studies was quantified (I2), and multiple meta-regressions were carried out to identify potential confounders.

Results

Within 4520 eligible studies, 51 articles fulfilling the selection criteria were included in the review, assessing 21 different prevention methods. A meta-analysis could only be performed on the 15 observational studies concerning magnesium supplementation (1841 patients), and showed a significant nephroprotective effect for all combined grades of CIA (OR 0.24, [0.19–0.32], I2 = 0.0%). This significant nephroprotective effect was also observed for grades 2 and 3 CIA (OR 0.22, [0.14–0.33], I2 = 0.0% and OR 0.25, [0.08–0.76], I2 = 0.0%, respectively).

Conclusion

While no method of prevention had so far demonstrated its indisputable efficacy, our results highlight the potential protective effect of magnesium supplementation on cisplatin-induced acute nephrotoxicity.

Trial Registration

This study is registered in PROSPERO, CRD42018090612.

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Acknowledgements

The authors thank Prof. Sylvester who sent us the raw data of his study and allowed us to integrate it in our work.

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Authors and Affiliations

  1. Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France

    Aghilès Hamroun, Rémi Lenain, Paul Chamley, Marc Hazzan, Mehdi Maanaoui & François Glowacki

  2. Faculty of Medicine, University of Paris Saclay, Paris, France

    Jean Joel Bigna

  3. Centre for Research in Epidemiology and Population Health (CESP), Paris Saclay University, Paris Sud University, Versailles Saint Quentin University, INSERM UMRS 1018, 94807, Villejuif, France

    Elodie Speyer

  4. Nephrology Department, CH Beuvry, Béthune, France

    Linh Bui

  5. Department of Toxicology and Genetic Pathologies, CHRU Lille, 59000, Lille, France

    Nicolas Pottier

  6. EA 4483-IMPECS-IMPact of Environmental ChemicalS on Human Health, Medicine Faculty, Research Department, University of Lille, 59045, Lille, France

    Christelle Cauffiez, Edmone Dewaeles & François Glowacki

  7. Pulmonary and Thoracic Oncology Department, University of Lille, INSERM U1189 OncoThAI, 59000, Lille, France

    Xavier Dhalluin & Arnaud Scherpereel

  8. INSERM, UMR995, 59000, Lille, France

    Marc Hazzan

Authors
  1. Aghilès Hamroun
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  2. Rémi Lenain
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  14. François Glowacki
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Contributions

Conceptualization: AH, RL, MM, JJB, FG. Supervision: AH, RL, MM, JJB, FG. Search strategy: AH, RL. Studies selection: AH, RL. Data curation: AH, RL, MM. Data synthesis and analysis: JJB. Data interpretation: AH, RL, MM, JJB, FG. Manuscript writing: AH, MM. Validation: AH, RL, MM, JJB, ES, PC, LB, NP, CC, ED, FG, MH, AS, and XD. Review and editing: ES, PC, LB, NP, CC, ED, FG, MH, AS, and XD (editing by an English native speaker: PC). Approved the final version of the manuscript: all the authors.

Corresponding author

Correspondence to Aghilès Hamroun.

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Conflict of interest

The authors declare that they have no conflicts of interest related to the content of this article (AH, RL, MM, JJB, ES, PC, LB, NP, CC, ED, FG, MH, AS, and XD).

Funding

This review received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Hamroun, A., Lenain, R., Bigna, J.J. et al. Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review and Meta-Analysis. Drugs 79, 1567–1582 (2019). https://doi.org/10.1007/s40265-019-01182-1

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