Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD

Background: In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal probrain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing end-stage renal disease (ESRD) in diabetic patients with CKD. Study Design: Prospective cohort study nested within a randomized clinical trial. Setting & Participants: Patients with type 2 diabetes, CKD (estimated glomerular filtration rate [eGFR], 20-60 mL/min/1.73 m ²), and anemia enrolled in TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy). Predictors: Serum levels of the cardiac biomarkers TnT and NT-pro-BNP. Outcomes: Incidence of ESRD and the composite of death or ESRD. Measurements: We measured TnT and NT-pro-BNP in baseline serum samples from the first 1,000 patients enrolled in TREAT. The relationship of these cardiac biomarker levels to the development of ESRD and death or ESRD was analyzed in multivariable regression models. Results: Detectable TnT (<0.01 ng/mL) was present in 45% of participants, and median NT-pro-BNP level was elevated at 605 pg/mL. Higher levels of both cardiac biomarkers were associated independently with higher rates of ESRD, as well as death or ESRD, and remained prognostically important after adjustment for eGFR, proteinuria, and other known predictors of CKD progression. The addition of cardiac biomarkers to a multivariable model for prediction of ESRD improved discrimination of those with and without an event by 16.9% (95% CI, 6.3%-27.4%). Limitations: Observational study in a clinical trial cohort; results require validation. Conclusions: In ambulatory patients with type 2 diabetes, anemia, and CKD, TnT and NT-pro-BNP levels frequently are elevated. These cardiac-derived biomarkers enhance prediction of ESRD beyond established risk factors. Measurement of TnT and NT-pro-BNP may improve the identification of patients with CKD who are likely to require renal replacement therapy, supporting a link between cardiac injury and the development of ESRD.