Biomarker-based acute kidney injury sub-phenotypes refine risk assessment in children undergoing cardiac surgery

Background Pediatric cardiac surgery-associated acute kidney injury (CS-AKI) is common with variable association with outcomes, possibly because transient serum creatinine (SCr) elevations are unrelated to kidney disease. Sub-phenotypes of CS-AKI with biomarker integration may provide prognostic enrichment. This study aims to determine if combining early postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr into sub-phenotypes strengthens associations with AKI and outcomes. We hypothesized that patients with early subclinical (uNGAL + , SCr −) or damage (uNGAL + , SCr +) CS-AKI would have more postoperative day 2–4 KDIGO-defined AKI and worse clinical outcomes than patients with early functional AKI (uNGAL − , SCr +). Methods Two-center prospective observational study evaluating combinations of early uNGAL (8–12 h from ICU admission, ≥ 150 ng/mL) and early postoperative (≤ 8 h of admission) KDIGO SCr-defined AKI to predict CS-AKI on postoperative days (POD) 2–4. Four CS-AKI phenotypes were derived (uNGAL − /SCr − ; uNGAL + /SCr − ; uNGAL − /SCr + and uNGAL + /SCr +). The primary outcome was POD2–4 KDIGO SCr-defined CS-AKI. Secondary outcomes included ventilator and intensive care unit-free days (maximum 28). Results Four hundred seventy-six patients (median age 4.8 [IQR 1.4–30.4] months, 39% female) were included. POD2–4 AKI occurred in 44 (9.2%). 27% were uNGAL + /SCr − and 0.4% ( n = 2) uNGAL + /SCr + . The adjusted odds of POD2–4 AKI was ninefold higher (aOR: 9.09, 95%CI: 3.84–21.53) in uNGAL + /SCr − when compared to uNGAL − /SCr − . uNGAL + /SCr − was associated with fewer ventilator-free (aOR: 0.30, 95%CI: 0.19–0.48) and ICU-free days (aOR: 0.41, 95%CI: 0.26–0.66) when compared to uNGAL − /SCr − . Conclusion Early postoperative uNGAL, regardless of SCr elevation, refines risk assessment for pediatric POD2–4 CS-AKI and associated morbidity, enabling earlier AKI identification and prognostics. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information