Regional clearance of amino-terminal pro-brain natriuretic peptide from human plasma

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AimsMechanisms for clearance of circulating amino-terminal pro-brain natriuretic peptide (NT-proBNP) remain poorly understood and are relevant to the clinical utility of NT-proBNP as a diagnostic and prognostic biomarker in cardiovascular disorders. We sought to determine site(s) of production and clearance of plasma NT-proBNP in the human circulation.Methods and resultsIn 120 subjects undergoing clinically indicated cardiac catheterization, blood samples were collected from arterial and multiple venous sites to measure transorgan gradients of plasma NT-proBNP. Clearance of plasma NT-proBNP occurred across kidney, liver, musculoskeletal, and head and neck tissues. Proportions of calculated total body NT-proBNP clearance were 55–65% across the kidney, 20–25% across the liver, 10–15% across musculoskeletal tissue, and 5–10% across the head and neck. Renal fractional extraction of NT-proBNP was unrelated to estimated glomerular filtration rate. Transorgan gradients, reflecting both renal and extra-renal NT-proBNP degradation, were correlated across multiple clearance sites within an individual.ConclusionPlasma NT-proBNP is cleared by multiple tissues in the human circulation with ∼55–65% of total clearance occurring in renal tissue. These data provide the first evidence for extra-glomerular clearance of NT-proBNP and suggest a common multisite clearance mechanism subject to generalized regulation. Renal NT-proBNP extraction was sustained in the face of even moderate levels of kidney dysfunction.

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