Clinical usefulness of B-type natriuretic peptide measurement: present and future perspectives.

Correspondence to: Professor Paulo M Bettencourt, Unidade Cuidados Intermédios Medicina, Hospital S Joaõ, Alameda Hernani Monteiro, 4200 Porto, Portugal; pbettfer@ esoterica.pt _________________________ T he identification of natriuretic peptides led to an explosion of basic and clinical investigations to clarify their physiology, pathophysiologic role in heart failure, and clinical usefulness. The knowledge base and emerging information on B-type natriuretic peptide (BNP) is plentiful but the consensus on its application is still sparse. The natriuretic peptide family comprises atrial natriuretic peptide (ANP), BNP, C-type natriuretic peptide (CNP), and D-type natriuretic peptide. ANP and BNP are synthesised in the heart, CNP is produced mainly in vessels, and D-type natriuretic peptide has been isolated in plasma and atrial myocardium. The precursor prohormone of each natriuretic peptide is encoded by a separate gene. BNP is a 108 amino acid pro-hormone that, after cleavage by the proteolytic enzyme furin, is separated into a 32 amino acid carboxi-terminal biologically active portion (BNP) and a 76 amino acid amino terminal part without biological activity (NT-proBNP) (fig 1). At present, there are four BNP assays commercially available for routine clinical practice. BNP can be assayed by a rapid fluorescence immunoassay (Biosite Diagnostic), an enzyme immunoassay (Abbott Laboratories), or a chemiluminescent immunoassay (Bayer Healthcare), and NT-proBNP can be measured by an electrochemiluminescent assay (Roche Diagnostics). ANP and BNP exert their effects through interaction with specific high affinity receptors on the target cells. Three effective receptors have been identified at target sites and kidneys. These receptors, located on cell membranes, although not reflecting their affinity for the different peptides, are termed: natriuretic receptor type A, natriuretic receptor type B, and type C—a clearance receptor. Most cardiovascular and renal effects of ANP and BNP result from cyclic guanylmonophosphate formation which acts as a second messenger responsible for the cellular physiological responses to natriuretic peptide stimulation. Natriuretic peptides are cleared from plasma by binding to natriuretic peptide receptors and through proteolysis by peptidases. NT-proBNP has a longer half life than BNP (118 v 18 minutes). Renal excretion is currently regarded as the main clearance mechanism of NT-proBNP. Relative concentrations of NT-proBNP and BNP may shift when healthy individuals are compared to heart failure patients. The significance of this shifting is not well understood, but changes in BNP production and shift in the degradation and half life caused by receptor regulation may be the aetiology of this observation.