Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19

Abstract

Rationale & objective: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19.

Study design: Prospective cohort study.

Setting & participants: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers.

Exposure: Twenty-six plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization.

Outcome: MAKE, defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days.

Analytical approach: Cox proportional hazards regression to associate biomarker level with MAKE. We additionally applied the least absolute shrinkage and selection operator (LASSO) and random forest regression for prediction modeling and estimated model discrimination with time-varying C index.

Results: The median length of stay for COVID-19 hospitalization was 9 (IQR, 5-16) days. In total, 95 patients (16%) experienced MAKE. Each 1 SD increase in soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 was significantly associated with an increased risk of MAKE (adjusted HR [AHR], 2.30 [95% CI, 1.86-2.85], and AHR, 2.26 [95% CI, 1.73-2.95], respectively). The C index of sTNFR1 alone was 0.80 (95% CI, 0.78-0.84), and the C index of sTNFR2 was 0.81 (95% CI, 0.77-0.84). LASSO and random forest regression modeling using all biomarkers yielded C indexes of 0.86 (95% CI, 0.83-0.89) and 0.84 (95% CI, 0.78-0.91), respectively.

Limitations: No control group of hospitalized patients without COVID-19.

Conclusions: We found that sTNFR1 and sTNFR2 are independently associated with MAKE in patients hospitalized with COVID-19 and can both also serve as predictors for adverse kidney outcomes.

Plain-language summary: Patients hospitalized with COVID-19 are at increased risk for long-term adverse health outcomes, but not all patients suffer long-term kidney dysfunction. Identification of patients with COVID-19 who are at high risk for adverse kidney events may have important implications in terms of nephrology follow-up and patient counseling. In this study, we found that the plasma biomarkers soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 measured in hospitalized patients with COVID-19 were associated with a greater risk of adverse kidney outcomes. Along with clinical variables previously shown to predict adverse kidney events in patients with COVID-19, both sTNFR1 and sTNFR2 are also strong predictors of adverse kidney outcomes.

Keywords: Acute kidney injury (AKI); COVID-19; biomarkers; chronic kidney disease (CKD).