Natriuretic Peptides in Chronic Kidney Disease

Background and objectives: B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are biomarkers of cardiovascular disease that is common in patients with chronic kidney disease (CKD). Conflicting data on the influence of glomerular filtration rate (GFR) on BNP and NT-proBNP levels in CKD may stem from failure to account fully for the effects of coexistent cardiac disease, dysfunction, and volume overload.Design, setting, participants, & measurements: Prospective head-to-head comparison of plasma BNP and NT-proBNP in ambulatory euvolemic CKD patients with normal LV ejection fraction and no manifest cardiac or vascular disease. GFR was estimated by the Modification of Diet in Renal Disease formula, BNP and NT-proBNP measured using Abbott AxSYM and Roche Elecsys assays, respectively, and cardiac morphology and function assessed by transthoracic echocardiography.Results: In 142 patients (42% female) of mean age 60 ± 11 yr, mean left ventricular ejection fraction was 71% ± 6%, GFR 38 ± 14 ml/min per 1.73 m², and median BNP and NT-proBNP level 59 and 311 pg/ml, respectively. Multivariate predictors of NT-proBNP level were GFR, β-blocker usage, LV mass index, and hemoglobin level. Plasma BNP was independently predicted by LV mass index and β-blocker usage but not GFR. In the 74 patients without diastolic dysfunction, there was a significant rise in NT-proBNP but not BNP as GFR declined.Conclusions: Unlike NT-proBNP, plasma BNP level is relatively independent of GFR. BNP may therefore be the more appropriate biomarker to screen for cardiac dysfunction in CKD.Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. Natriuretic peptides (NPs), biomarkers of myocardial dysfunction (1), offer the potential for early detection and risk stratification of cardiac disease, as evident in emergency department (2) and community (3,4) settings. This screening utility could be extended to CKD patients asymptomatic of cardiovascular disease.However, the precise influence of CKD on circulating levels of B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP), the two commonly used NPs in clinical practice, continues to be debated. Dependence of plasma BNP on glomerular filtration rate (GFR) has been reported among patients with and without heart failure (HF) (5,6), but this relationship may not be independent of cardiac or volume-related factors (7,8). The data on NT-proBNP in renal dysfunction are more concordant but were derived from populations that included patients with myocardial infarction, reduced left ventricular (LV) ejection fraction (LVEF), or HF (9,10). Indeed, most studies examining the impact of renal dysfunction on NPs uniformly included such patients (5,6,8–10). Recent Doppler myocardial imaging studies have shown that even HF patients with normal LVEF have reduced LV contractility compared with controls (11,12).To limit confounding by cardiac dysfunction or volume overload, we prospectively constituted a clinically euvolemic CKD cohort without symptoms or history of cardiac disease and normal LVEF and regional function. We measured circulating levels of both NPs, hypothesizing that, in these patients, BNP can be shown to be relatively independent of GFR compared with NT-proBNP if cardiac and loading factors can be comprehensively accounted for.