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

https://doi.org/10.1016/j.jacc.2008.11.032Get rights and content
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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 FEBNPwas 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-proBNPwas 0.16 (IQR 0.09 to 20) for left and 0.18 (IQR 0.12 to 0.22) for right kidneys. The FEBNPcorrelated 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 FEBNPand FENT-proBNPcorrelated strongly with each other (left: r = 0.66; right: r = 0.60; p < 0.001 for both), left and right FENT-proBNP/BNPratios 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

Cited by (0)

Roche Diagnostics supplied NT-proBNP reagents for this study. Dr. van Kimmenade is sponsored by a research fellowship grant from the Interuniversity Cardiology Institute of the Netherlands (ICIN). Dr. Januzzi is supported in part by the Balson Scholar fund; and has received grant funding, consulting income, and/or speaking honoraria from Roche Diagnostics, Siemens, Inverness Medical, and Critical Diagnostics. Dr. Pinto has received grant funding and speaking honoraria from Roche Diagnostics.