Tubular Injury Biomarkers to Detect Gentamicin-Induced Acute Kidney Injury in the Neonatal Intensive Care Unit.
OBJECTIVE
We evaluated whether urinary excretion of tubular injury markers could be useful for early detection of gentamicin (GM)-induced renal damage in neonates.


METHODS
We conducted a prospective, observational trial in neonates admitted to the neonatal intensive care unit (26 GM treated, 20 control). Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and π- and α-glutathione-S-transferase (GSTP1-1 and GSTA1-1) were measured every 2 hours during admission and compared with serum creatinine (sCr) and urine output.


RESULTS
Nine neonates developed AKI during the course of the study. The peak in excretion of urinary biomarkers preceded the peak in sCr (p < 0.0001). GM administration resulted in a more pronounced increase of sCr compared with control (13 [12-28] vs. 10 µmol/L [8.5-17]; p < 0.05). The urinary excretion of NAG (178 [104-698] vs. 32 ng/mol Cr [9-82]; p < 0.001) and NGAL (569 [168-1,681] vs. 222 ng/mol Cr [90-497]; p < 0.05) was higher in the GM group compared with control and preceded the peak of sCr and urine output decrease.


CONCLUSIONS
GM administration to neonates is associated with renal damage reflected by a more pronounced increase in sCr preceded by urinary excretion of biomarkers. Urinary biomarkers may be useful for earlier identification of renal injury in neonates.
Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Diana
D
Jansen
Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Esther
E
Peters
Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Suzanne
S
Heemskerk
Department of Pediatric Nephrology, Radboud university medical center, Nijmegen, The Netherlands.
Linda
L
Koster-Kamphuis
Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Martijn P W J M
MP
Bouw
Department of Gastroenterology, Radboud university medical center, Nijmegen, The Netherlands.
Hennie M J
HM
Roelofs
Haemoscan, Groningen, The Netherlands.
Wim
W
van Oeveren
Department of Neonatology, Radboud university medical center, Nijmegen, The Netherlands.
Arno F J
AF
van Heijst
Department of Intensive Care Medicine, Radboud university medical center, Nijmegen, The Netherlands.
Peter
P
Pickkers
D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D000209:Acute-Phase Proteins / Q000652:urine; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001238:Asphyxia Neonatorum; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015331:Cohort Studies; D000013:Congenital Abnormalities; D003404:Creatinine / Q000097:blood; D005260:Female; D005839:Gentamicins / Q000009:adverse effects*; D005865:Gestational Age; D051549:Glutathione S-Transferase pi / Q000652:urine; D005982:Glutathione Transferase / Q000652:urine; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus
D000209:Acute-Phase Proteins; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D005839:Gentamicins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D003404:Creatinine; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D000118:Acetylglucosaminidase