Renal Clearance of B-Type Natriuretic Peptide and Amino Terminal Pro-B-Type Natriuretic Peptide A Mechanistic Study in Hypertensive Subjects

Objectives This study sought to compare the renal clearance mechanisms of B-type natriuretic peptide (BNP) and amino terminal pro-B-type natriuretic peptide (NT-proBNP). Background The small molecular weight proteins (SMWPs) BNP and NT-proBNP both inversely correlate with glomerular filtration rate (GFR). Whether this association is causal or confounding is unknown and has been the basis of widespread speculation. Methods We combined measurements of BNP and NT-proBNP concentrations in the renal arteries and veins of 165 subjects undergoing renal arteriography with invasive renal plasma flow (RPF) measurements and echocardiography. Fractional extraction (FE) of BNP and NT-proBNP was computed. Results The BNP and NT-proBNP concentrations correlated similarly to GFR (r = -0.35 and r = -0.30, respectively; p < 0.001 for both) but the NT-proBNP/BNP serum ratio was negatively associated with GFR (r = -0.21, p = 0.008). Median FEBNP was 0.21 (interquartile range [IQR] 0.16 to 0.22) for left and 0.22 (IQR 0.17 to 0.29) for right kidneys. Median FENT-proBNP was 0.16 (IQR 0.09 to 20) for left and 0.18 (IQR 0.12 to 0.22) for right kidneys. The FEBNP correlated with GFR (left: r = 0.26, p = 0.008; right: r = 0.21, p = 0.03) as did FENT-proBNP (left: r = 0.25, p = 0.005; right: r = 0.20, p = 0.02). Although FEBNP and FENT-proBNP correlated strongly with each other (left: r = 0.66; right: r = 0.60; p = 0.001 for both), left and right FENT-proBNP/BNP ratios were not influenced by GFR (r = 0.10, p = 0.30 and r = 0.08, p = 0.43, respectively). Multivariate analyses confirmed that FE was not independently associated with BNP or NT-proBNP concentrations. Conclusions Contrary to widespread belief (but in line with the renal physiology of SMWP), BNP and NT-proBNP are equally dependent on renal function for their clearance. (J Am Coll Cardiol 2009; 53: 884-90) (C) 2009 by the American College of Cardiology Foundation