Introduction: Cardiac biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin-T (Hs-cTnT) are good prognostic indicators of long-term clinical cardiovascular outcomes in patients with chronic kidney disease. However, the clinical utility of combined biomarkers in predicting death and cardio-renal outcomes in patients with CKD remains unclear. This study examined the prognostic accuracy and incremental value of, NT-proBNP and Hs-cTnT for all-cause mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD) in non-dialysis dependent chronic kidney disease (NDD-CKD) patients.

Methods: Data from 1946 individuals with NDD-CKD prospectively included in the Salford Kidney Study was used to investigate the associations between NT-proBNP and Hs-cTnT with study endpoints. Hazards ratio or sub-hazards ratio and 95% confidence intervals (95%CI) were estimated using multivariate Cox-regression and competing risk models. The discriminatory power of NT-proBNP and Hs-cTnT along with kidney biomarkers (RBMs: eGFR and UACR) and Framingham Risk score (FRS) were calculated using Harrell's C-index. Endpoint-specific risk scores were generated using regression coefficients obtained in a training dataset and confirmed in a validation one.

Results: During median follow-up of 71.5 months, 931 (47.8%) deaths, 553 (28.4%) MACE and 554 (28.5%) ESKD events occurred. Baseline NT-proBNP and Hs-cTnT elevations were associated with significant increased risk of mortality, MACE and ESKD independently of FRS and RBMs. Combining NT-proBNP, Hs-cTnT, and FRS yielded the highest prognostic accuracy for all-cause mortality and MACE (respective C-statistics:0.713; 95%CI:0.695-0.731, and 0.697;95%CI:0.673-0.721,), while combining NT-proBNP, and Hs-cTnT with RBMs performed best at predicting ESKD (C-statistics:0.821; 95%CI: 0.786-0.826).

Conclusions: In NDD-CKD patients, NT-proBNP and Hs-cTnT are predictors of all-cause mortality, MACE, and ESKD, independently of RBMs. Combining NT-proBNP and Hs-cTnT with RBMs outperformed risk prediction for ESKD compared to RBMs used alone or in combination.