Supplementary Material for: Prognostic Significance of Asymptomatic Brain Natriuretic Peptide Elevation at Nephrology Referral in Patients with Chronic Kidney Disease

Background: It is unclear whether asymptomatic elevation of brain natriuretic peptide (BNP) is associated with cardiovascular events (CVEs) or heart failure (HF) in predialysis chronic kidney disease (CKD) patients. Methods: We measured BNP in 482 asymptomatic predialysis patients with CKD stages 2–5 at nephrology referral between August 2004 and October 2010, and followed them prospectively to investigate the prognostic significance of BNP using Cox models and receiver operating characteristic (ROC) analyses. The primary composite end point was the time to death or the first nonfatal CVEs. Secondary end points included CVEs including sudden death, HF and all-cause death. Results: The median age was 67 years (male, 67.4%; diabetic nephropathy, 33.4%), and estimated glomerular filtration rate was 20.1 mL/min/1.73 m². The primary end point occurred in 92 patients. CVEs including sudden death, HF and all-cause death occurred in 66, 35, and 54 patients, respectively during a median follow-up period of 37.7 months. Multivariate analyses showed that BNP level was significantly associated with the primary end point (hazard ratio [HR] 1.241; 95% CI 1.020–1.511; p = 0.031), CVEs (HR 1.337; 95% CI 1.067–1.675; p = 0.012) and HF (HR 1.489; 95% CI 1.059–2.091; p = 0.022), but not associated with all-cause death (HR 1.081; 95% CI 0.829–1.410; p = 0.565). The ROC curves showed that the optimal predictive BNP levels for the primary end point, CVEs and HF were 92.5, 127.0, and 274.6 (pg/mL) respectively. Conclusion: Asymptomatic elevation of BNP is strongly predictive for CVEs and HF, which might help to integrate cardio-renal risk stratification in predialysis CKD patients.