ARTICLE: Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19
AUTHORS: Steven Menez, Steven G Coca, Dennis G Moledina, Yumeng Wen, Lili Chan, Heather Thiessen-Philbrook, Wassim Obeid, Brian T Garibaldi, Evren U Azeloglu, Ugochukwu Ugwuowo, C John Sperati, Lois J Arend, Avi Z Rosenberg, Madhurima Kaushal, Sanjay Jain, F Perry Wilson, Chirag R Parikh; TRIKIC Consortium
JOURNAL: Am J Kidney Dis. 2023 May 30;S0272-6386(23)00648-0. doi: 10.1053/j.ajkd.2023.03.010. Online ahead of print.
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 and participants: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers.
Exposures: 26 plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization.
Outcomes: Major adverse kidney events (MAKE), defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days.
Analytic 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 nine (IQR: 5-16) days. In total, 95 (16%) patients 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), while 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-indices 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: TNFR1 and sTNFR2 are independently associated with MAKE in patients hospitalized with COVID-19, and can both also serve as predictors for adverse kidney outcomes.
Keywords: Index words: COVID-19; acute kidney injury (AKI); biomarkers; chronic kidney disease (CKD).
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