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Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19
Steven Menez1, Steven G Coca2, Dennis G Moledina3
1Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Insights
Plasma biomarkers soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 predict major adverse kidney events (MAKE) in hospitalized COVID-19 patients. These findings aid in identifying high-risk individuals for targeted nephrology care and counseling.
Area of Science:
- Nephrology
- Infectious Diseases
- Biomarker Discovery
Background:
- Hospitalized COVID-19 patients face elevated risks of major adverse kidney events (MAKE).
- Predictive biomarkers are crucial for identifying at-risk individuals for timely intervention.
- Existing research highlights the need for specific markers to stratify kidney risk in COVID-19.
Purpose of the Study:
- To identify plasma biomarkers that predict MAKE in hospitalized COVID-19 patients.
- To assess the predictive performance of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) for adverse kidney outcomes.
Main Methods:
- Prospective cohort study involving 576 hospitalized COVID-19 patients.
- Analysis of 26 plasma biomarkers, including sTNFR1 and sTNFR2, from initial blood samples.
- Utilized Cox regression, LASSO, and random forest modeling to associate biomarkers with MAKE (KDIGO stage 3 AKI, dialysis, or mortality).
Main Results:
- 16% of patients experienced MAKE.
- Increased levels of sTNFR1 and sTNFR2 were significantly associated with higher MAKE risk (aHRs ~2.3).
- Individual biomarkers demonstrated strong predictive capability (C-indices ~0.80-0.81), with combined models achieving higher discrimination (C-indices ~0.84-0.86).
Conclusions:
- Soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 are independent predictors of MAKE in COVID-19 patients.
- These biomarkers can aid in identifying individuals at high risk for adverse kidney outcomes post-COVID-19 hospitalization.
- Findings support the integration of sTNFR1 and sTNFR2 into risk assessment protocols for enhanced nephrology follow-up.
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.
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