title: A systematic meta-analysis on the efficacy of pre-clinically tested nephroprotectants at preventing aminoglycoside nephrotoxicity.
abstract: Nephrotoxicity limits the use of aminoglycoside antibiotics. Kidney damage is produced mainly in the renal tubule due to an inflammatory and oxidative process. At preclinical level, many drugs and natural products have been tested as prospective protectors of aminoglycoside nephrotoxicity. The main objective of this work was to make a systematic literature review of preclinical studies about aminoglycoside nephrotoxicity protection and a statistical analysis based on the meta-analysis methodology. Studies published up to January 2016 were identified. After applying inclusion criteria, 54 studies were chosen. The size of the experimental groups, means and standard deviations of data on renal function (i.e. plasma creatinine and blood urea nitrogen [BUN] concentrations) were extracted and registered in a database. The studies were grouped according to the mechanism of nephroprotection and their route of administration. The Mean Difference (95% confidence interval) was calculated for each study and group. 40 of 54 products tested produced an amelioration of aminoglycoside nephrotoxicity based on creatinine results. Also a dose dependent protective effect was observed (both in creatinine and BUN). Products orally administered were more effective than via i.p. Products with attributed antioxidant activity were the most used and those which proved statistically significant nephroprotection as a class effect. Aminoglycoside tubular reuptake inhibitors, excretion inducers and calcium channel blockers also showed a promising and rather homogeneous class tendency towards nephroprotection, although more research is necessary to obtain solid and conclusive results, based on a larger number of studies.
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, University of Salamanca, 37007, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL)-Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL), Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Valladolid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Vicente-Vicente
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, University of Salamanca, 37007, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL)-Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL), Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Valladolid, Spain.
authors.forename: Alfredo G
authors.initials: AG
authors.lastname: Casanova
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, University of Salamanca, 37007, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL)-Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL), Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Valladolid, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Hernández-Sánchez
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, University of Salamanca, 37007, Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Valladolid, Spain.
authors.forename: Moisés
authors.initials: M
authors.lastname: Pescador
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, University of Salamanca, 37007, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL)-Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL), Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Valladolid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Hernández
authors.affiliation: Unidad de Toxicología, Departamento de Fisiología y Farmacología, University of Salamanca, 37007, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL)-Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL), Salamanca, Spain; Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Valladolid, Spain. Electronic address: amorales@usal.es.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Morales
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D010936:Plant Extracts / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D010936:Plant Extracts; D020011:Protective Agents
keywords: AKI; Creatinine; Forest plot; Gentamicin; Nephroprotection; Urea