Renal clearance of B-type natriuretic peptide and amino terminal pro-B-type natriuretic peptide a mechanistic study in hypertensive subjects.
OBJECTIVE
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.
van Kimmenade
Roland R J
RR
Department of Cardiology, University Hospital Maastricht, the Netherlands. rolandvank@hotmail.com
Januzzi
James L
JL
Bakker
Jaap A
JA
Houben
Alphonse J
AJ
Rennenberg
Roger
R
Kroon
Abraham A
AA
Crijns
Harry J G M
HJ
van Dieijen-Visser
Marja P
MP
de Leeuw
Peter W
PW
Pinto
Yigal M
YM
D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood* / Q000378:metabolism; D011446:Prospective Studies; D011859:Radiography; D012077:Renal Artery / Q000000981:diagnostic imaging; D017595:Renal Plasma Flow
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain