Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19

Abstract

Rationale & objective: Acute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19.

Study design: Prospective cohort study.

Setting & participants: Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020.

Exposure: 19 urinary biomarkers of injury, inflammation, and repair.

Outcome: Composite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings.

Analytical approach: Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome.

Results: Out of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine.

Limitations: Small sample size with low number of composite outcome events.

Conclusions: Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

Keywords: Acute kidney injury (AKI); COVID-19 prognosis; chronic kidney disease (CKD); coronavirus disease 2019 (COVID-19); death; dialysis; epidermal growth factor (EGF); inflammatory marker; kidney injury molecule 1 (KIM-1); monocyte chemoattractant protein 1 (MCP-1); neutrophil gelatinase-associated lipocalin (NGAL); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); subclinical AKI; tubular injury; urinalysis; urinary biomarkers; urine microscopy.