Clinical Implementation of Urinary NGAL Testing for Diagnosing Acute Kidney Injury in an Academic Tertiary Care Medical Centre.

Abstract

Background: Differentiating functional acute kidney injury (AKI) from structural/intrinsic AKI with tubular injury remains a clinical challenge. Urinary NGAL (uNGAL) has shown promise in distinguishing these conditions. This study evaluated the implementation of uNGAL in a heterogeneous medical cohort at an academic tertiary care center in Ireland over a three-year period.

Methods: A retrospective audit was conducted from 2020-2023. Standard clinical data around the time of AKI and uNGAL request were recorded. Blinded case adjudication of the differential diagnosis of AKI cause using the standard clinical information (but not urine NGAL results) was performed by two expert Nephrologists. Analysis of uNGAL focused on the accuracy in differentiating adjudicated (Intra-renal) AKI from Non-intrinsic AKI (Pre-renal & Post-renal).

Results: A total of 323 uNGAL tests were performed, with 292 AKI cases adjudicated. Intrinsic AKI cases had significantly higher uNGAL and uNGAL/Cr levels than non-intrinsic cases (p < 0.001), including after excluding UTI cases. uNGAL (AUC 0.71; 95% CI: 0.65-0.77) and uNGAL/Cr (AUC 0.73; 95% CI: 0.67-0.79) showed moderate discriminative performance. uNGAL (threshold 150 ng/ml) had high sensitivity (0.87) and negative predictive value (0.82). uNGAL/Cr was similar at the 288 ng/mg threshold. Discriminative performance improved for uNGAL and uNGAL/Cr, but not for serum creatinine, fractional excretion of sodium (FENa), or serum urea, after excluding UTI cases. Both uNGAL (aOR 2.05; 95% CI: 1.59-2.71) and uNGAL/Cr (aOR 2.07; 95% CI: 1.64-2.68) were independently associated with intrinsic AKI. Adding these biomarkers to a logistic regression model significantly improved discrimination performance (AUC 0.79; 95% CI: 0.76-0.84; p = 0.0116).

Conclusions: The use of uNGAL improved the discriminative accuracy of differential diagnosis of AKI in clinical practice by differentiating intrinsic AKI from non-intrinsic. Specificity was low at the manufacturer's recommended threshold (150ng/ml), but the sensitivity and NPV were high in all analyses. These findings support the clinical utility of uNGAL at the 150ng/ml threshold as a "rule-out" test for intrinsic AKI, thereby helping to direct management toward functional (pre-renal) or obstructive (post-renal) causes when uNGAL is negative.