Utility of Cardiac Biomarkers (N-Terminal Pro-B-Type Natriuretic Peptide and Hs-Troponin-T) in Predicting Mortality, Cardiovascular, and Renal Outcomes in Patients with Chronic Kidney Disease.

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 (CKD). 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 event (MACE), and end-stage kidney disease (ESKD) in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients.

Methods: Data from 1,946 individuals with NDD-CKD prospectively included in the Salford Kidney Study were used to investigate the associations between NT-proBNP and Hs-cTnT with study endpoints. Hazard ratio or sub-hazard ratio and 95% confidence intervals (95% CIs) were estimated using multivariate Cox-regression and competing risk models. The discriminatory power of NT-proBNP and Hs-cTnT along with kidney biomarkers (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. 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 eGFR and uACR performed best at predicting ESKD (C-statistics: 0.821; 95% CI: 0.786-0.826).

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