BNP and NT-proBNP heart failure blood tests produce markedly different results depending on which lab instrument is used, because there are no universal standards for measuring these peptide biomarkers.
No standard existsThere is no certified reference material for calibrating BNP or NT-proBNP assays, making results method-dependent
What the researchers found
Different commercial immunoassays for BNP and NT-proBNP produce markedly different results that are not comparable to each other. There is currently no certified reference material or standardized calibration approach for either biomarker, meaning that diagnostic cut-off values are method-dependent rather than universal.
The lack of equivalence stems partly from the complex nature of circulating BNP-related peptides — BNP exists in multiple forms in blood (precursors, fragments, glycosylated variants), and different assays detect different combinations of these forms.
Why it matters
BNP and NT-proBNP blood tests are used millions of times yearly to diagnose heart failure, guide treatment decisions, and assess prognosis. If different lab instruments give different numbers for the same blood sample, doctors may misinterpret results — especially when patients switch hospitals or labs. Standardizing these peptide measurements is essential for consistent cardiac care worldwide.
The numbers in context
BNP discovered in 1988 · Multiple commercial assays with non-comparable results · No certified reference material exists · No standardized calibration procedures
How the study worked
This is a review chapter in Advances in Clinical Chemistry that synthesizes data on the molecular forms of circulating BNP-related peptides, compares the specificity and performance of existing commercial BNP and NT-proBNP immunoassays, and evaluates potential approaches for standardization including reference materials and measurement procedures.
Who was studied
Review of clinical immunoassay data and peptide biochemistry studies
What this study cannot tell us
As a review, this paper does not present new experimental data. The standardization solutions discussed are proposals rather than implemented systems. The review was published in 2018 and the standardization landscape may have evolved since.
How to read the evidence
This is a comprehensive review published in a respected clinical chemistry series, synthesizing comparative assay data and peptide biochemistry. While authoritative, it proposes solutions rather than validating them, and the field may have progressed since 2018.
When this study was published
Published in 2018, this review addresses a standardization gap that remains partially unresolved. Some progress on harmonization has been made since, but full standardization of natriuretic peptide assays has not yet been achieved.
The bigger picture
This standardization challenge affects every hospital using natriuretic peptide testing for heart failure — which is essentially all of them. The problem illustrates a broader issue in peptide diagnostics: when the target molecule exists in multiple forms (precursors, fragments, modified variants), a single number can mean different things depending on which forms the assay detects. Solving this for BNP/NT-proBNP could create a template for standardizing other peptide biomarker measurements.
Questions still open
- Has a certified reference material for BNP or NT-proBNP been developed since this 2018 review?
- Could mass spectrometry-based methods replace immunoassays to provide more standardized BNP measurements?
- How many clinical misdiagnoses or treatment errors result from the current lack of assay equivalence?
Common questions
What are BNP and NT-proBNP and why are they tested?
Why do different labs give different BNP results for the same patient?
Read the original research
Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and Complex Nature of Circulating BNP-Related Peptides.
Advances in clinical chemistry, 85, 1-30
Citation
Semenov, Alexander G; Feygina, Evgeniya E. (2018). Standardization of BNP and NT-proBNP Immunoassays in Light of the Diverse and Complex Nature of Circulating BNP-Related Peptides.. Advances in clinical chemistry, 85, 1-30. https://doi.org/10.1016/bs.acc.2018.02.001