Urinary biomarkers of kidney injury and inflammation may identify patients at high risk for severe acute kidney injury (AKI), dialysis, and death during COVID-19 illness, a new study finds.

In the prospective study, investigators examined the levels of 19 urinary biomarkers in 153 patients hospitalized with COVID-19 at Yale and Johns Hopkins medical centers from April to June 2020. Of the cohort, 24 patients (15.7%) experienced the primary composite outcome of stage 3 AKI, dialysis, or death within 60 days of hospital admission.

Compared with normal reference values, a 2-fold higher level of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein (MCP-1), and kidney injury molecule 1 (KIM-1) were significantly associated with 1.3-, 1.4-, and 2.0-fold increased risks for the primary composite outcome, Chirag R. Parikh, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues reported in the American Journal of Kidney Diseases. Combinations of urinary biomarkers were more discriminating than the individual biomarkers, the investigators found. The presence of viral RNA in the urine and urine microscopy score did not predict adverse kidney outcomes.


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These findings coincide with several recent studies investigating the value of serum and urinary biomarkers in predicting COVID-19-related AKI.

The investigators of the current study found that the degree of tubular injury and inflammation during COVID-19 illness was not markedly higher compared with other common settings of AKI (detailed in the TRIAL-AKI study). The biomarker evidence suggests that both proximal and distal tubular damage may be occurring in COVID-19-associated AKI, according to the investigators.

Subclinical AKI, defined by elevations in urinary biomarkers such as NGAL and IL-18, was present in 30%-50% of patients hospitalized with COVID-19 who did not have impairment in kidney function, the investigators also reported. A comparator group awaiting cardiac surgery had lower levels of these markers. Previous research has found that subclinical AKI is also associated with adverse outcomes. Patients with COVID-19 illness “may represent a very high-risk group who will require close follow-up of kidney function upon discharge,” Dr Parikh’s team emphasized.

Higher epidermal growth factor levels, a marker of repair after muscle and kidney tissue injury, was significantly associated with a 39% decreased risk of the primary outcome, the investigators reported.

“These findings may improve the risk stratification of patients admitted with COVID-19.”

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

Reference

Menez S, Moledina DG, Thiessen-Philbrook H, et al; the TRIKIC Consortium investigators. Prognostic significance of urinary biomarkers in patients hospitalized with COVID-19. Am J Kidney Dis. 2022 Feb;79(2):257-267. doi:10.1053/j.ajkd.2021.09.008