Integration of urinary neutrophil gelatinase-associated lipocalin with serum creatinine delineates acute kidney injury phenotypes in critically ill children

Purpose: Acute kidney injury (AKI)is prevalent in critically ill patients and associated with poor outcomes. Current AKI diagnostics— changes to serum creatinine (SCr)and urine output— are imprecise. Integration of injury biomarkers with SCr may improve diagnostic precision. Methods: We performed a secondary analysis of a study of critically ill children. Measurements of urine neutrophil gelatinase-associated lipocalin (uNGAL)and SCr samples from ICU admission facilitated the creation of four groups for comparison, based on elevation of SCr from baseline and reference NGAL cut-off value: uNGAL-/SCr-, uNGAL+/SCr-, uNGAL-/SCr + and uNGAL+/SCr+. The primary outcome assessed was AKI severity on Day 3. Results: 178 children were studied. Compared to uNGAL-/SCr-, uNGAL+/SCr- patients had increased risk for all-stage Day 3 AKI (≥ KDIGO stage 1)(OR 3.83, [1.3–11.3], p =.025). Compared to uNGAL-/SCr+, uNGAL+/SCr + patients had increased risk for severe Day 3 AKI (≥ KDIGO stage 2)(OR 12, [1.4–102], p =.018). The only patients to suffer all-stage Day 3 AKI and mortality were uNGAL+ (3.2% uNGAL+/SCr-; 6.5% uNGAL+/SCr+). Conclusions: Unique biomarker combinations on admission are predictive of distinct Day 3 AKI severity phenotypes. These classifications may enable a more personalized approach to the early management of AKI. Expanded study in larger populations is warranted.