Association of Urine Biomarkers With Acute Kidney Injury and Fluid Overload in Infants After Cardiac Surgery: A Single Center Ancillary Cohort of the Steroids to Reduce Systemic Inflammation After Infant Heart Surgery Trial

Abstract

OBJECTIVES: To examine the association between three perioperative urine biomarker concentrations (urine cystatin C [uCysC], urine neutrophil gelatinase-associated lipocalin [uNGAL], and urine kidney injury molecule 1 [uKIM-1]), and cardiac surgery-associated acute kidney injury (CS-AKI) and fluid overload (FO) in infants with congenital heart disease undergoing surgery on cardiopulmonary bypass. To explore how urine biomarkers are associated with distinct CS-AKI phenotypes based on FO status. DESIGN: Ancillary prospective cohort study. SETTING: Single U.S. pediatric cardiac ICU. PATIENTS: Infants less than 1 year old enrolled in the Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial (NCT03229538) who underwent heart surgery from June 2019 to May 2020 and opted into biomarker collection at a single center. Infants with preoperative CS-AKI were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty infants met inclusion criteria. Median (interquartile) age at surgery was 103 days (5.5–161 d). Modified Kidney Disease Improving Global Outcomes-defined CS-AKI was diagnosed in 22 (55%) infants and 21 (53%) developed FO. UCysC and uNGAL peaked in the early postoperative period and uKIM-1 peaked later. In unadjusted analysis, bypass time was longer, and Vasoactive-Inotropic Score at 24 hours was higher in infants with CS-AKI. On multivariable analysis, higher uCysC (odds ratio [OR], 1.023; 95% CI, 1.004–1.042) and uNGAL (OR, 1.019; 95% CI, 1.004–1.035) at 0–8 hours post-bypass were associated with FO. UCysC, uNGAL, and uKIM-1 did not significantly correlate with CS-AKI. In exploratory analyses of CS-AKI phenotypes, uCysC and uNGAL were highest in CS-AKI+/FO+ infants. CONCLUSIONS: In this study, uCysC and uNGAL in the early postoperative period were associated with FO at 48 hours. UCysC, uNGAL, and uKIM-1 were not associated with CS-AKI. Further studies should focus on defining expected concentrations of these biomarkers, exploring CS-AKI phenotypes and outcomes, and establishing clinically meaningful endpoints for infants post-cardiac surgery.