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

Kevin A Pettit; Katherine F Melink; Jeffrey A Alten; Stuart L Goldstein; Nicholas Ollberding; Megan SooHoo; Emily Sullivan; Huaiyu Zang; Natalja L Stanski; Katja M Gist

doi:10.1007/s00467-024-06541-z

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

Pediatr Nephrol. 2024 Sep 27. doi: 10.1007/s00467-024-06541-z. Online ahead of print.

Affiliations

¹ Department of Pediatrics, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, CO, USA. kevin.pettit@childrenscolorado.org.
² Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³ Department of Pediatrics, Children's Hospital Colorado, University of Colorado Anschutz Medical Center, Aurora, CO, USA.

PMID: 39331076
DOI: 10.1007/s00467-024-06541-z

Abstract

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.

Keywords: AKI diagnostic phenotypes; Cardiac surgery; Persistent AKI; uNGAL.