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CLINICAL RESEARCH: BIOMARKERS

Renal Clearance of B-Type Natriuretic Peptide and Amino Terminal Pro-B-Type Natriuretic Peptide

A Mechanistic Study in Hypertensive Subjects

Roland R.J. van Kimmenade, MD, PhD^_*,,_*, James L. Januzzi, Jr, MD, FACC, Jaap A. Bakker, MSc, Alphonse J. Houben, PhD, Roger Rennenberg, MD, Abraham A. Kroon, MD, PhD, Harry J.G.M. Crijns, MD, PhD^_*, Marja P. van Dieijen-Visser, PhD, Peter W. de Leeuw, MD, PhD and Yigal M. Pinto, MD, PhD^||

^_* Department of Cardiology, University Hospital Maastricht, the Netherlands
Department of Clinical Chemistry, University Hospital Maastricht, the Netherlands
Department of Internal Medicine, University Hospital Maastricht, the Netherlands
Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts
^|| Heart Failure Research Center, Academic Medical Centre, Amsterdam, the Netherlands

Manuscript received July 8, 2008; revised manuscript received September 26, 2008, accepted November 16, 2008.

^_* Reprint requests and correspondence: Dr. Roland R. J. van Kimmenade, Department of Cardiology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands (Email: rolandvank{at}hotmail.com).

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 FE_BNP 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 FE_NT-proBNP was 0.16 (IQR 0.09 to 20) for left and 0.18 (IQR 0.12 to 0.22) for right kidneys. The FE_BNP correlated with GFR (left: r = 0.26, p = 0.008; right: r = 0.21, p = 0.03) as did FE_NT-proBNP (left: r = 0.25, p = 0.005; right: r = 0.20, p = 0.02). Although FE_BNP and FE_NT-proBNP correlated strongly with each other (left: r = 0.66; right: r = 0.60; p < 0.001 for both), left and right FE_{NT-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.

Key Words: natriuretic peptides • NT-proBNP • BNP • kidney • renal function

Abbreviations and Acronyms   BNP = B-type natriuretic peptide   CKD = chronic kidney disease   FE = fractional extraction   GFR = glomerular filtration rate   IQR = interquartile range   MAP = mean arterial pressure   NT-proBNP = amino terminal pro-B-type natriuretic peptide   RBF = renal blood flow   RPF = renal plasma flow   SMWP = small molecular weight protein

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