Aghilès Hamroun1, Rémi Lenain2, Jean Joel Bigna3, Elodie Speyer4, Linh Bui5, Paul Chamley2, Nicolas Pottier6, Christelle Cauffiez7, Edmone Dewaeles7, Xavier Dhalluin8, Arnaud Scherpereel8, Marc Hazzan2,9, Mehdi Maanaoui2, François Glowacki2,7. 1. Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France. aghiles.hamroun@gmail.com. 2. Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France. 3. Faculty of Medicine, University of Paris Saclay, Paris, France. 4. 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. 5. Nephrology Department, CH Beuvry, Béthune, France. 6. Department of Toxicology and Genetic Pathologies, CHRU Lille, 59000, Lille, France. 7. EA 4483-IMPECS-IMPact of Environmental ChemicalS on Human Health, Medicine Faculty, Research Department, University of Lille, 59045, Lille, France. 8. Pulmonary and Thoracic Oncology Department, University of Lille, INSERM U1189 OncoThAI, 59000, Lille, France. 9. INSERM, UMR995, 59000, Lille, France.
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.
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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