Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Renal Injury Following Extracorporeal Membrane Oxygenation

Pediatr Crit Care Med. 2015 Sep;16(7):663-70. doi: 10.1097/PCC.0000000000000476.

Abstract

Objective: To evaluate the course of urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 levels in young children during extracorporeal membrane oxygenation and concomitant continuous hemofiltration. Furthermore, to evaluate whether these levels predict outcome.

Design: Prospective observational cohort study from July 2010 to July 2013.

Setting: ICU of a level III university children's hospital.

Patients: Thirty-one extracorporeal membrane oxygenation-treated children up to 1 year were included.

Interventions: None.

Measurements and main results: Patients were weaned from extracorporeal membrane oxygenation after a median of 162 hours (interquartile range, 83-304). Throughout the study, 58% of the patients met the criteria for acute kidney injury (i.e., Risk Injury Failure Loss End-Stage Renal Disease-Risk or higher defined as an increase in serum creatinine corresponding to ≥ 150% when compared with age-specific reference values). Levels of both biomarker patterns changed significantly throughout extracorporeal membrane oxygenation (urinary neutrophil gelatinase-associated lipocalin, p < 0.001 and urinary kidney injury molecule-1, p = 0.005, linear mixed model analyses). Urinary neutrophil gelatinase-associated lipocalin levels were already high before extracorporeal membrane oxygenation, whereas urinary kidney injury molecule-1 levels increased throughout the first extracorporeal membrane oxygenation day and peaked at 12-24 hours. Also, urinary neutrophil gelatinase-associated lipocalin levels at 12-24 hours of extracorporeal membrane oxygenation therapy were higher among patients with acute kidney injury post extracorporeal membrane oxygenation (p = 0.002, Mann-Whitney U test). Biomarker levels did not differ between survivors and nonsurvivors.

Conclusions: The increased urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 levels confirm that renal tubular damage occurs in critically ill infants in need of extracorporeal membrane oxygenation. The fact that the maximal urinary neutrophil gelatinase-associated lipocalin levels were measured 24 hours earlier than urinary kidney injury molecule-1 supports the use of biomarker combinations rather than a single biomarker to identify patients at risk of acute kidney injury. Finally, since urinary neutrophil gelatinase-associated lipocalin levels at 12-24 hours of extracorporeal membrane oxygenation therapy were associated with acute kidney injury post extracorporeal membrane oxygenation, this marker may facilitate more timely adjustment of therapeutic interventions.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / urine
  • Acute-Phase Proteins / urine*
  • Biomarkers / urine
  • Cohort Studies
  • Critical Illness
  • Extracorporeal Membrane Oxygenation / adverse effects*
  • Female
  • Hospitals, University
  • Humans
  • Infant
  • Infant, Newborn
  • Kidney Function Tests
  • Lipocalin-2
  • Lipocalins / urine*
  • Male
  • Netherlands
  • Prospective Studies
  • Proto-Oncogene Proteins / urine*

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins