Urine test predicts kidney injury and death in COVID-19

Xu, K.; Shang, N.; Levitman, A.; Corker, A.; Kudose, S.; Yaeh, A.; Neupane, U.; Stevens, J.; Mohan, S.; Sampogna, R.; D'Agati, V.; Kiryluk, K.; Barasch, J.

Background: Kidney injury is common in COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We hypothesized that molecular markers of tubular injury could diagnose COVID-19 associated kidney damage and predict its clinical course. Methods: This is a prospective cohort study of 444 consecutive COVID-19 patients (43.9% females, 20.5% African American, 54.1% Latinx) in Columbia University's Emergency Department at the peak of the New York pandemic (March-April 2020). Urine and blood were collected simultaneously at admission (median time of day 0, IQR 0-2 days) and within 1 day of a positive SARS-CoV-2 test in 70% of patients. Biomarker assays were blinded to clinical data. Results: Urinary NGAL (uNGAL) was strongly associated with AKI diagnosis (267{+/-}301 vs. 96{+/-}139 ng/mL, P=1.6x10-10). uNGAL >150ng/mL had 80% specificity and 75% sensitivity to diagnose AKIN stage 2 or higher. uNGAL quantitatively predicted the duration of AKI and outcomes, including death, dialysis, shock, and longer hospital stay. The risk of death increased 73% per standard deviation of uNGAL [OR (95%CI): 1.73 (1.29-2.33), P=2.8x10-4] and was independent of baseline SCr, co-morbidities, and proteinuria [adjusted OR (95%CI): 1.51 (1.10-2.11), P=1.2x10-2]. Proteinuria and uKIM-1 also indicated tubular injury, but were not diagnostic of AKI. Typically, distal nephron segments transcribe NGAL, but in COVID-19 biopsies with widespread acute tubular injury (ATI), NGAL expression overlapped KIM-1 in proximal tubules. Conclusion: uNGAL predicted the diagnosis, duration, and severity of AKI and ATI, as well as hospital stay, dialysis, shock, and death in patients with acute COVID-19.