Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and Complex Nature of Circulating BNP-Related Peptides

Adv Clin Chem. 2018:85:1-30. doi: 10.1016/bs.acc.2018.02.001. Epub 2018 Mar 3.


Brain natriuretic peptide (BNP) and the N-terminal fragment of the BNP precursor (NT-proBNP) are widely used as heart failure (HF) biomarkers. Since the discovery of BNP in 1988, much effort has been allocated to the precise detection of BNP and NT-proBNP levels for reliable HF diagnostics. As a result, measurements of these biomarkers are globally accepted and used in clinical practice for the diagnosis of acute and chronic HF, risk stratification, and monitoring response to therapy. Several immunoassays specific for BNP and NT-proBNP are currently commercially available. Recent comparative studies show that there are marked differences between different BNP and NT-proBNP assays and platforms, and the results of measurements are not comparable enough. The lack of equivalence between the assays complicates the interpretation of the results and renders the cut-off points for diagnostic decisions to be method dependent. Presently, there is no agreement on what kind of BNP or NT-proBNP standard should be used for calibration, and a certified reference material as well as reference measurement procedures are lacking. The aim of this chapter is to summarize the available data on the complex nature of BNP-related peptides, specificity for existing BNP and NT-proBNP immunoassays, and to discuss potential approaches for standardization of BNP and NT-proBNP measurements.

Keywords: ANP; BNP; Calibrator; Glycosylation; Immunoassay; NT-proBNP; Natriuretic peptide; Neprilysin; Standardization; proBNP.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / blood
  • Glycosylation
  • Heart Failure / blood
  • Heart Failure / diagnosis
  • Heart Failure / therapy
  • Humans
  • Immunoassay / instrumentation
  • Immunoassay / methods*
  • Immunoassay / standards
  • Natriuretic Peptide, Brain / analysis
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / analysis
  • Peptide Fragments / blood*
  • Protein Processing, Post-Translational


  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain