Elevated Neutrophil Gelatinase-Associated Lipocalin Is Associated With the Severity of Kidney Injury and Poor Prognosis of Patients With COVID-19

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

doi:10.1016/j.ekir.2021.09.005

Elevated Neutrophil Gelatinase-Associated Lipocalin Is Associated With the Severity of Kidney Injury and Poor Prognosis of Patients With COVID-19

Kidney Int Rep. 2021 Dec;6(12):2979-2992. doi: 10.1016/j.ekir.2021.09.005. Epub 2021 Oct 8.

Authors

Affiliations

¹ Department of Medicine, Columbia University, New York, New York, USA.
² Department of Pathology, Columbia University, New York, New York, USA.
³ Department of Emergency Medicine, Columbia University, New York, New York, USA.
⁴ Department of Epidemiology, Columbia University, New York, New York, USA.

Abstract

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 acute kidney injury (AKI) in those with COVID-19 infection.

Methods: This is a prospective cohort observational study consisting of 444 consecutive patients with SARS-CoV-2 enrolled in the Columbia University emergency department (ED) at the peak of the pandemic in New York (March 2020-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, interquartile range: 0-2 days), and urine biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA) and a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores.

Results: Admission urinary neutrophil gelatinase-associated lipocalin (uNGAL) level was associated with AKI diagnosis (267 ± 301 vs. 96 ± 139 ng/ml, P < 0.0001) and staging; uNGAL levels >150 ng/ml had 80% specificity and 75% sensitivity to diagnose AKI stages 2 to 3. Admission uNGAL level quantitatively associated with prolonged AKI, dialysis, shock, prolonged hospitalization, and in-hospital death, even when admission SCr level was not elevated. The risk of dialysis increased almost 4-fold per SD of uNGAL independently of baseline SCr, comorbidities, and proteinuria (odds ratio [OR] [95% CI]: 3.59 [1.83-7.45], P < 0.001). In the kidneys of those with COVID-19, NGAL mRNA expression broadened in parallel with severe histopathologic injury (ATI). Conversely, low uNGAL levels at admission ruled out stages 2 to 3 AKI (negative predictive value: 0.95, 95% CI: 0.92-0.97) and the need for dialysis (negative predictive value: 0.98, 95% CI: 0.96-0.99). Although proteinuria and urinary (u)KIM-1 were implicated in tubular injury, neither was diagnostic of AKI stages.

Conclusion: In the patients with COVID-19, uNGAL level was quantitatively associated with histopathologic injury (ATI), loss of kidney function (AKI), and severity of patient outcomes.

Keywords: COVID-19; KIM1; NGAL; acute kidney injury; acute tubular injury; dialysis; kidney biopsy.

Abstract

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