Urine Olfactomedin 4 Predicts Furosemide Response and Kidney Replacement Therapy in Critically Ill Children

To test whether urine olfactomedin 4 (uOLFM4) can predict furosemide responsiveness in patients at high risk for acute kidney injury (AKI) early in the PICU course. A secondary outcome was prediction of kidney replacement therapy (KRT) initiation in this cohort.

Prospective observational cohort study.

Two quaternary care PICUs.

Two hundred forty PICU patients with a renal angina index greater than or equal to 8 and a urine sample collected on PICU days 0-1. Fifty-six patients received a furosemide dose on PICU days 1-4 and 44 received KRT.

None.

uOLFM4 was measured via enzyme-linked immunosorbent assay. Urine neutrophil gelatinase-associated lipocalin (uNGAL) was measured via particle-enhanced turbidimetric immunoassay by the clinical laboratory. We compared groups using Mann-Whitney U tests or Kruskal-Wallis tests and calculated area under the receiver operating characteristic curve for performance of uOLFM4 and uNGAL to predict furosemide responsiveness on PICU days 1-4 and KRT receipt. Median (interquartile range) uOLFM4 and uNGAL concentrations were higher in patients who were furosemide nonresponsive (uOLFM4 694 ng/mL [214-1478 ng/mL] vs. 139 ng/mL [46-529 ng/mL]; p = 0.0004 and uNGAL 1149 ng/mL [204-2284 ng/mL] vs. 53 ng/mL [50-1533 ng/mL]; p = 0.0076) and higher in patients who received KRT. uOLFM4 and uNGAL had similar moderate discriminatory ability to predict furosemide responsiveness (area under the curve, 0.77 [95% CI, 0.65-0.90]; p = 0.0005 and 0.71 [95% CI, 0.57-0.85]; p = 0.0088, respectively). uOLFM4 of 156 ng/mL had 59% sensitivity, 96% specificity, a positive predictive value of 64%, and negative predictive value (NPV) of 95% to predict furosemide responsiveness.

In critically ill children at high risk for AKI, both uOLFM4 and uNGAL have moderate discriminatory ability to predict furosemide responsiveness and KRT receipt on the first day of PICU stay. The NPV greater than or equal to 95% for uOLFM4 for both outcomes make it a promising candidate for implementation into clinical decision support to facilitate early KRT initiation decision-making.