Association Between Urine Biomarkers and Acute Kidney Injury in Patients With COVID-19

For patients hospitalized with COVID-19, urinary neutrophil gelatinase-associated lipocalin (uNGAL) concentration was found to be a significant predictor of severe acute kidney injury (AKI) and worse clinical outcomes, according to results of a prospective cohort observational study published in Kidney International Reports.

Investigators analyzed data from consecutive patients with confirmed SARS-CoV-2 infection admitted to the Columbia University emergency department (ED) in New York between March and April 2020. The investigators measured molecular biomarkers uNGAL and urinary kidney injury molecule 1 (uKIM-1), which have shown sensitive and real-time detection of AKI from urine samples collected on admission via enzyme-linked immunosorbent assay (ELISA) and a novel dipstick that measures uNGAL at the bedside. They analyzed kidney biopsy specimens to determine biomarker RNA and histopathologic acute tubular injury (ATI) scores. Primary outcomes were serum creatinine-based AKI, AKI Network (AKIN) stage, and the duration of consistently increased concentrations of serum creatinine among patients in both groups. Patients with SARS-CoV-2 infection were compared against a cohort of patients without the infection who were recruited in an identical manner between June 2017 and January 2019.

Among patients in both the COVID-19 (n=444) and control groups (n=426), 43.9% and 42.7% were women, 20.5% and 18% were Black, 54.1% and 24.0% were Hispanic, and the mean age was 63.7 and 60.3 years. Respectively. Patients (n=4) with end-stage kidney disease were excluded from the study.

Among patients with SARS-CoV-2 infection, uNGAL concentrations were associated with an increased risk for AKI (P <.0001), increasing in a stepwise fashion with AKIN stages (P <.0001). In addition, uNGAL concentrations greater than 150 ng/mL were associated with a specificity and sensitivity of 80% and 75%, respectively, in diagnosing AKIN stages 2 to 3. The investigators found that patients with decreased uNGAL concentrations on admission had a decreased risk for stage 2 and 3 AKI (negative predictive value (NPV), 0.95; 95% CI, 0.92-0.97) and the need for dialysis (NPV, 0.98; 95% CI, 0.96-0.99). This association was found to be independent of age, sex, race, ethnicity, baseline serum creatinine concentration, proteinuria, and other comorbidities.

In a subgroup analysis of 198 patients with COVID-19 without evidence of AKI on admission to the ED, uNGAL concentrations were increased among those who subsequently developed stage 1 to 3 AKI within 7 days compared with those who did not develop AKI (P <.05).

The risk for requiring dialysis increased almost 4-fold per standard deviation of uNGAL concentrations among patients in the COVID-19 group, independent of baseline serum creatinine concentrations, comorbidities, and proteinuria (odds ratio, 3.59; 95% CI, 1.83-7.45; P <.001). In addition, uNGAL concentrations were found to be quantitatively associated with prolonged AKI, shock, prolonged hospitalization, and in-hospital death, including among those with increased baseline serum creatinine concentrations on admission. The kidneys of patients with COVID-19 exhibited broad NGAL mRNA expression in parallel with severe histopathologic injury (ATI). In addition, neither proteinuria nor uKIM-1 were diagnostic of AKI or AKIN stages among patients in the COVID-19 group.

The investigators found that uKIM-1, proteinuria, and proximal tubule cells were increased among patients in the COVID-19 group compared with those in the control group. In addition, uNGAL concentrations were associated with AKIN stages among patients in both groups, whereas uKIM-1 was not associated with AKIN stages among those in either group.

This study was limited by its use of serum creatinine concentrations as the gold standard for diagnosing AKI due to the inability to assess baseline creatinine concentrations among 69 patients.

“The association of uNGAL [concentrations] with AKI and ATI provides the possibility of a sensitive diagnostic strategy that bypasses the delays and insensitivity of [serum creatinine concentrations],” the investigators noted. In addition, “the absence of [increased] uNGAL concentrations essentially ruled out the need for dialysis and identified patients at [a decreased] risk [of] death,” the investigators concluded.

Disclosure: One author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Xu K, Shang N, Levitman A, et al. Elevated NGAL is associated with the severity of kidney injury and poor prognosis of patients with COVID-19. Kidney Int Rep. Published online October 8, 2021. doi:10.1016/j.ekir.2021.09.005