Background: Soluble tumor necrosis factor receptor (sTNFR)1, sTNFR2, and plasma kidney injury molecule 1 (KIM1) are associated with kidney events in patients with and without diabetes. However, their associations with clinical outcomes when obtained pre operatively have not been explored.
Methods: The TRIBE AKI cohort study is a prospective, multicenter, cohort study of high risk adults undergoing cardiac surgery. We assessed the associations between pre operative concentrations of plasma sTNFR1, sTNFR2, and KIM1 and post operative long term outcomes including mortality, cardiovascular events, and chronic kidney disease (CKD) incidence or progression, ascertained after discharge.
Results: Among 1378 participants included in the analysis with a median follow up period was 6.7 (IQR 4.0,7.9), 434 (31%) patients died, 256 (19%) experienced cardiovascular events and out of 837 with available long term kidney function data, 30% developed CKD. After adjustment for clinical covariates, each log increase in biomarker concentration was independently associated with mortality with 95% CI adjusted hazard ratios (aHRs) of 3.0 (2.3,4.0), 2.3 (1.8,2.9) and 2.0 (CI 1.6,2.4) for sTNFR1, sTNFR2 and KIM1, respectively. For cardiovascular events, the 95%CI aHRs were 2.1 (1.5,3.1), 1.9 (1.4,2.6) and 1.6 (1.2,2.1) for sTNFR1, sTNFR2 and KIM1, respectively. For CKD events, the aHRs were 2.2 (1.5,3.1) for sTNFR1, 1.9 (1.3,2.7) for sTNFR2, and 1.7 (1.3,2.3) for KIM1. Despite the associations, each of the biomarkers alone or in combination failed to result in robust discrimination on an absolute basis or compared to a clinical model.
Conclusion: sTNFR1, sTNFR2, and KIM1 were independently associated with longitudinal outcomes after discharge from a cardiac surgery hospitalization including death, cardiovascular and CKD events when obtained pre operatively in high risk individuals. Pre operative plasma biomarkers could serve to assist during the evaluation of patients in whom cardiac surgery is planned.