Quality Specifications for B-Type Natriuretic Peptide Assays

Abstract

Background:The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. Methods: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. Results: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. Conclusions: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

Comparison of the Diagnostic Accuracy of Brain Natriuretic Peptide (BNP) and the N-Terminal Part of the Propeptide of BNP Immunoassays in Chronic and Acute Heart Failure: A Systematic Review

“…The analytical performance and clinical results of ECLIA methods differ greatly compared with other commercial or in-house methods for NT-proBNP measurement (Tables 1 and 2). For these reasons, our data confirm that the cutoff values are method dependent (3,7,8,37 ).…”

Natriuretic Peptides and Analytical Barriers

“…The stability of the sample is method dependent with different stabilities of the epitopes targeted by the specific assay. BNP is unstable when collected in glass tubes because of activation of kallikreins and this degradation may be dependent on the specificities of antibodies used in the measurement method (40 ). It is recommended that BNP blood samples be collected in plastic tubes only.…”

“…The NT-proBNP assay is relatively stable during storage in serum, heparinized plasma, or EDTA plasma when stored at room temperature or 4°C for at least 72 h or for up to 1 year when stored at Ϫ80°C. Additionally, for both BNP and NT-proBNP assays, validation for the effect of freeze-thaw cycles upon stability needs to be performed (40 ).…”

Reference Change Values for Brain Natriuretic Peptides Revisited

“…In the presence of K ϩ , internal fluorescence quenching is reduced, and fluorescence emission is proportional to the K ϩ concentration in the specimen. The sensor displays negligible interference from pH, calcium, or sodium (5 ).…”