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Mechanism-based urinary biomarkers to identify the potential for aminoglycoside-induced nephrotoxicity in premature neonates: a proof-of-concept study.

McWilliam, SJ; Antoine, DJ; Sabbisetti, V; Turner, MA; Farragher, T; Bonventre, JV; Park, BK; ... Pirmohamed, M; + view all (2012) Mechanism-based urinary biomarkers to identify the potential for aminoglycoside-induced nephrotoxicity in premature neonates: a proof-of-concept study. PLOS One , 7 (8) , Article e43809. 10.1371/journal.pone.0043809. Green open access

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Abstract

Premature infants are frequently exposed to aminoglycoside antibiotics. Novel urinary biomarkers may provide a non-invasive means for the early identification of aminoglycoside-related proximal tubule renal toxicity, to enable adjustment of treatment and identification of infants at risk of long-term renal impairment. In this proof-of-concept study, urine samples were collected from 41 premature neonates (≤ 32 weeks gestation) at least once per week, and daily during courses of gentamicin, and for 3 days afterwards. Significant increases were observed in the three urinary biomarkers measured (Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG)) during treatment with multiple courses of gentamicin. When adjusted for potential confounders, the treatment effect of gentamicin remained significant only for KIM-1 (mean difference from not treated, 1.35 ng/mg urinary creatinine; 95% CI 0.05-2.65). Our study shows that (a) it is possible to collect serial urine samples from premature neonates, and that (b) proximal tubule specific urinary biomarkers can act as indicators of aminoglycoside-associated nephrotoxicity in this age group. Further studies to investigate the clinical utility of novel urinary biomarkers in comparison to serum creatinine need to be undertaken.

Type: Article
Title: Mechanism-based urinary biomarkers to identify the potential for aminoglycoside-induced nephrotoxicity in premature neonates: a proof-of-concept study.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0043809
Publisher version: http://dx.doi.org/10.1371/journal.pone.0043809
Language: English
Additional information: © McWillliam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The authors would like to acknowledge financial support from the Medical Research Council (grant number G0700654) and to the Royal Society for an International Travelling Fellowship awarded to DJA. JVB is supported by US National Institutes of Health grants DK39773 and DK072381. SMcW is an MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics which is funded by the Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca and the Medical Evaluation Unit.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Acetylglucosaminidase, Acute Kidney Injury, Acute-Phase Proteins, Aminoglycosides, Anti-Bacterial Agents, Biological Markers, Female, Gentamicins, Humans, Infant, Newborn, Infant, Premature, Lipocalins, Male, Membrane Glycoproteins, Proto-Oncogene Proteins, Receptors, Virus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1375458
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