Systematic review and meta-analysis of the efficacy of clinically tested protectants of cisplatin nephrotoxicity

  • Alfredo G. Casanova
  • María Teresa Hernández-Sánchez
  • Francisco J. López-Hernández
  • Carlos Martínez-Salgado
  • Marta Prieto
  • Laura Vicente-VicenteEmail author
  • Ana Isabel Morales
Clinical Trial



Cisplatin is a potent antineoplastic drug that has been widely used to treat a number of solid tumors. However, a high incidence of renal damage observed in patients has led researchers to search for alternate strategies that prevent or at least reduce the cisplatin-induced nephrotoxicity. The objective of the present study was to conduct a systematic review and a subsequent meta-analysis to evaluate and identify compounds with effective antitumor activity and lesser side effects that could provide protection against cisplatin-induced nephrotoxicity.


The study included all placebo-controlled trials published up to December 2017 that met the inclusion criteria. A total of 22 articles were finally included to extract the following information: number of patients, doses of cisplatin and protectant, qualitative (acute kidney injury incidence) and quantitative (plasma creatinine, blood urea nitrogen, and creatinine clearance) indicators of renal function. The odds ratio or the mean difference (95% confidence interval) of each parameter was calculated for each study and group of studies.


The results of this meta-analysis show that there is great variability in the nephroprotective capacity of a variety of products evaluated. Of all the compounds tested, only magnesium sulfate and cystone were found to exert protective effects. However, more studies need to be conducted to confirm these results.


The administration of 1 g of Mg i.v. seems to be the best strategy for the prevention of cisplatin nephrotoxicity.


Nephroprotection Cisplatin Meta-analysis Clinical Magnesium Cystone 


Funding information

M. Teresa Hernández-Sánchez is a recipient of a predoctoral fellowship from the Junta de Castilla y León (Spain) and the European Social Fund from the European Commission. Research from the authors’ laboratory supporting part of the information incorporated into this article has been funded by grants from Instituto de Salud Carlos III (PI17/01979, DT15S/00166, and PI15/01055, PI14/01776), co-funded by FEDER, and Retic (RD016/0009/0025) REDINREN-FEDER funds, Junta de Castilla y León, Consejería de Sanidad (BIO/SA66/15, BIO/SA20/14); and Consejería de Educación, (SA359U14).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alfredo G. Casanova
    • 1
    • 2
    • 3
    • 4
  • María Teresa Hernández-Sánchez
    • 1
    • 2
    • 3
    • 4
  • Francisco J. López-Hernández
    • 1
    • 2
    • 3
    • 4
  • Carlos Martínez-Salgado
    • 1
    • 2
    • 3
    • 4
  • Marta Prieto
    • 1
    • 2
    • 3
    • 4
  • Laura Vicente-Vicente
    • 1
    • 2
    • 3
    • 4
    Email author
  • Ana Isabel Morales
    • 1
    • 2
    • 3
    • 4
  1. 1.Unidad de Toxicología, Departamento de Fisiología y FarmacologíaUniversity of SalamancaSalamancaSpain
  2. 2.Instituto de Investigación Biomédica de Salamanca (IBSAL)-Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL)SalamancaSpain
  3. 3.Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD)SalamancaSpain
  4. 4.Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic)ValladolidSpain

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