Elevated NGAL is Associated with the Severity of Kidney Injury and Poor Prognosis of Patients with COVID-19

Xu, Katherine; Shang, Ning; Levitman, Abraham; Corker, Alexa; Kudose, Satoru; Yaeh, Andrew; Neupane, Uddhav; Stevens, Jacob; Sampogna, Rosemary; Mills, Angela M.; D’Agati, Vivette; Mohan, Sumit; Kiryluk, Krzysztof; Barasch, Jonathan

INTRODUCTION: Loss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission were associated with AKI in those with COVID-19 infection. METHODS: This is a prospective cohort observational study consisting of 444 consecutive SARS-CoV-2 patients enrolled in the Columbia University Emergency Department at the peak of New York’s pandemic (March-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, IQR 0-2 days) and urine biomarkers analyzed by ELISA and by a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores. RESULTS: Admission uNGAL was associated with AKI diagnosis (267±301 vs. 96±139 ng/mL, P < 0.0001) and staging; uNGAL levels >150ng/mL demonstrated 80% specificity and 75% sensitivity to diagnose AKI-stage 2-3. Admission uNGAL quantitatively associated with prolonged AKI, dialysis, shock, prolonged hospitalization, and in-hospital death, even when admission SCr was not elevated. The risk of dialysis increased almost 4-fold per standard deviation of uNGAL independently of baseline SCr, co-morbidities, and proteinuria [OR(95%CI): 3.59 (1.83-7.45), P < 0.001]. In COVID-19 kidneys, NGAL mRNA expression broadened in parallel with severe histopathological injury (ATI). Conversely, low uNGAL levels at admission ruled out stage 2-3 AKI (NPV 0.95, 95%CI: 0.92-0.97) and the need for dialysis (NPV: 0.98, 95%CI: 0.96-0.99)). While proteinuria and uKIM-1 implicated tubular injury, neither were diagnostic of AKI stages. CONCLUSIONS: In COVID-19 patients, uNGAL quantitatively associated with histopathological injury (ATI), the loss of kidney function (AKI), and the severity of patient outcomes.