BACKGROUND: Increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with increased cardiovascular mortality in chronic hemodialysis patients. Previous studies focused on prevalent dialysis patients and examined single measurements of NT-proBNP in time. METHODS: We measured NT-proBNP concentrations in 2990 incident hemodialysis patients to examine the risk of 90-day and 1-year mortality associated with baseline NT-proBNP concentrations. In addition, we calculated the change in concentrations after 3months in a subset of 585 patients to examine the association between longitudinal changes in NT-proBNP and subsequent mortality. RESULTS: Increasing quartiles of NT-proBNP were associated with amonotonic increase in 90-day [quartile 1, referent; from quartile 2 to quartile 4, hazard ratio (HR) 1.7-6.3, P < 0.001] and 1-year (quartile 1, referent; from quartile 2 to quartile 4, HR 1.7-4.9, P < 0.001) all-cause mortality. After multivariable adjustment, these associations remained robust. When examined using a multivariable fractional polynomial, increased NT-proBNP concentrations were associated with increased 90-day (HR per unit increase in log NT-proBNP 1.5, 95% CI 1.3-1.7) and 1-year (HR per unit increase in log NT-proBNP 1.4, 95% CI 1.3-1.5) allcause mortality. In addition, patients with the greatest increase in NT-proBNP after 3 months of dialysis had a 2.4-fold higher risk of mortality than those with the greatest decrease in NT-proBNP. CONCLUSIONS: NT-proBNP concentrations are independently associated with mortality in incident hemodialysis patients. Furthermore, the observation that longitudinal changes in NT-proBNP concentrations were associated with subsequent mortality suggests that monitoring serial NT-proBNP concentrations may represent a novel tool for assessing adequacy and guiding therapy in patients initiating hemodialysis. © 2008 American Association for Clinical Chemistry.