Pre-operative kidney biomarkers and risks for death, cardiovascular and chronic kidney disease events after cardiac surgery: the TRIBE-AKI study

Background — Soluble tumor necrosis factor receptor (sTNFR)1, sTNFR2, and plasma kidney injury molecule-1 (KIM-1) 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 KIM-1 and post-operative long-term outcomes including mortality, cardiovascular events, and chronic kidney disease (CKD) incidence or progression after discharge.

Results — Among 1378 participants included in the analysis with a median follow-up period of 6.7 (IQR 4.0–7.9) years, 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 (1.6–2.4) for sTNFR₁, sTNFR₂, and KIM-1, 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 KIM-1, 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 KIM-1. 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.

Conclusions — TNFR₁, sTNFR₂, and KIM-1 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.