Supplementary Material for: The utility of urinary NGAL as an alternative for serum creatinine to detect acute kidney injury (AKI) in infants exposed to nephrotoxic medications in the NICU

Introduction
Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby NINJA (Nephrotoxic Injury Negated by Just-in-time Action) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program.
Methods
This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to seven days of NTM exposure plus two days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs.
Results
The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3%-100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39-4.13).
Discussion/Conclusion
We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.