Mechanism-Based Urinary Biomarkers to Identify the Potential for Aminoglycoside-Induced Nephrotoxicity in Premature Neonates: A Proof-of-Concept Study
McWilliam, Stephen J.
Antoine, Daniel J.
Turner, Mark A.
Park, B. Kevin
Smyth, Rosalind L.
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CitationMcWilliam, Stephen J., Daniel J. Antoine, Venkata Sabbisetti, Mark A. Turner, Tracey Farragher, Joseph V. Bonventre, B. Kevin Park, Rosalind L. Smyth, and Munir Pirmohamed. 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): e43809.
AbstractPremature 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.
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