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Pediatric Nephrology
Published in: Pediatric Nephrology 11/2017

Open Access 01-11-2017 | Review

Aminoglycoside-induced nephrotoxicity in children

Authors: Stephen J McWilliam, Daniel J Antoine, Rosalind L Smyth, Munir Pirmohamed

Published in: Pediatric Nephrology | Issue 11/2017

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Abstract

Aminoglycoside antibiotics, in particular gentamicin and tobramycin, are still commonly used in paediatric clinical practice. These drugs cause nephrotoxicity, which particularly affects the proximal tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides via the multi-ligand receptor megalin. Recent epidemiological studies, using more widely accepted definitions of acute kidney injury (AKI), have suggested that AKI may occur in between 20 and 33 % of children exposed to aminoglycosides. A consensus set of phenotypic criteria for aminoglycoside-induced nephrotoxicity have recently been published. These are specifically designed to provide robust phenotyping for pharmacogenomic studies, but they can pave the way for standardisation for all clinical studies. Novel renal biomarkers, in particular kidney injury molecule-1, identify aminoglycoside-induced proximal tubular injury earlier than traditional markers and have shown promise in observational studies. Further studies need to demonstrate a clear association with clinically relevant outcomes to inform translation into clinical practice. Extended interval dosing of aminoglycosides results in a reduction in nephrotoxicity, but its use needs to become more widespread. Inhibition of megalin-mediated endocytosis by statins represents a novel approach to the prevention of aminoglycoside-induced nephrotoxicity which is currently being evaluated in a clinical trial. Recommendations for future directions are provided.
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Metadata
Title
Aminoglycoside-induced nephrotoxicity in children
Authors
Stephen J McWilliam
Daniel J Antoine
Rosalind L Smyth
Munir Pirmohamed
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 11/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3533-z

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