The effect of gender on aminoglycosideassociated nephrotoxicity

Abstract

Aims: The kidney disease improving global outcomes (KDIGO) clinical practice guidelines for acute kidney injury (AKI) has endorsed the widely held belief that female gender is a risk factor for aminoglycoside-associated nephrotoxicity (AAN). In contrast, female gender is protective in animal models. In light of this dichotomy, we sought to explore this relationship in greater detail. Methods: We performed a meta-analysis of studies published between 1978 and 2015 which examined aminoglycoside nephrotoxicity and provided gender-specific data. Results: 24 studies were identified that provided univariate gender-specific data. The incidence of AAN did not differ between the sexes (odds ratio (OR) for females vs. males 1.00 (0.81, 1.22), p = 0.97, n = 5,980). Twelve studies utilized logistic regression analysis with gender as a covariate. Meta-analysis of the 5 studies that utilized multivariate analysis and reported gender-specific OR found no effect of gender on the risk of AAN (OR 0.99 (0.58, 1.69), p = 0.96, n = 2,994). Similarly, gender was not an independent risk factor for AAN in the remaining 7 studies that utilized multivariate analysis with gender as a covariate but failed to report gender-specific OR (n = 1,636). Discussion: Our meta-analysis contradicts the generally held consensus that female gender is an independent risk factor for the development of AAN. Our findings may have much wider implications insofar as AAN cannot be used as an example to support the conclusion of the KDIGO Clinical Practice Guidelines that female gender is an independent risk factor for AKI.