Prognostic stratification in a diabetic kidney disease trial using plasma concentrations of soluble tumor necrosis factor receptor 1

Background: Concentration of circulating soluble tumor necrosis factor receptor 1 is associated with faster progression in patients with diabetic kidney disease based on data obtained from large longitudinal cohort studies. A cutpoint of 4.3 ng/mL baseline plasma concentration was identified to stratify patients and predict clinical outcome. We set out to test the prognostic utility of this cutpoint in a randomized clinical trial. Methods: Soluble tumor necrosis factor receptor 1 concentration was measured across plasma samples from Joslin cohort and selonsertib trial cohort. Estimated glomerular filtration rate slope was calculated using a patient-specific linear regression model based on serum creatinine concentration and compared between the cohorts. Kidney-related events were plotted using Kaplan-Meier estimates for both cohorts. Results: Participants from both the clinical study cohort and the observational cohort showed an inverse relationship between baseline plasma concentrations of tumor necrosis factor receptor 1 and estimated glomerular filtration rate. When stratified based on baseline soluble tumor necrosis factor receptor 1 cutpoint, higher probability of experiencing a clinical event was found in patients with levels of soluble tumor necrosis factor receptor 1 exceeding 4.3 ng/mL in either of the cohorts. Conclusion: We demonstrated the prognostic utility of plasma concentrations of circulating soluble tumor necrosis factor receptor 1 in identifying individuals with diabetic kidney disease at an elevated risk of progressive kidney function decline in a randomized clinical study setting. This data supports previous findings from large observational cohorts and supports the use of this marker as a reliable predictor of disease outcome.