Proficiency testing project for brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) immunoassays: the CardioOrmocheck study

Abstract

Background: We organized and conducted a proficiency testing study (CardioOrmocheck) to evaluate the differences in analytical performance of brain natriuretic peptide (BNP) and N-terminal proBNP (NTproBNP) immunoassays. Results: The mean total variability for BNP (50.6 %CV) was significantly higher than that for NT-proBNP (8.4 %CV). In addition, the mean variability due to differences between-methods (46.4 %CV) comprised the majority of the total variability for BNP. Betweenmethod variability for BNP comprised, on average, 84% of total variability, while the within-method variability comprised an average of 20.2 %CV. On the contrary, for NT-proBNP the within-method variability (7.3 %CV) represented the majority of total variability (average 75%), while between-method variability was smaller (4.1 %CV). Imprecision around the cut-off value showed marked differences among methods, especially for BNP immunoassay methods. In addition, BNP methods were affected by large systematic differences, for example an average 2.7-fold difference between Access and ADVIA Centaur methods, while agreement between NT-proBNP methods was better (an average 1.2-fold difference between Dimension and ECLIA on the Elecsys methods).

Natriuretic Peptides and Analytical Barriers

“…There are only minor differences between the commercial NTproBNP assays with variation across methods that is Ͻ10%. Despite this standardization, however, assay harmonization remains incomplete (32 ). The International Collaborative of NT-proBNP Study involving 1256 patients proposed a cutoff value for NT-proBNP assays below or above 125 ng/L.…”

New issues on measurement of B-type natriuretic peptides

“…NT-proBNP is more stable in vivo and in vitro: it has a higher molecular mass and a longer biological plasma half-live and a lower intra-individual biological variation (Table 1). Furthermore, data from external quality assessment studies demonstrated that immunoassays methods for NT-proBNP share on average better analytical performances (including better sensitivity and imprecision) than those of BNP [1][2][3][4]. Furthermore, these studies also reported that there are large systematic differences (up to twofolds) between the BNP values measured by the most popular immunoassay methods, whereas the NT-proBNP methods show a between-method variability lower than 20% because they use calibrators and materials from the same manufacturer [3,4].…”

“…Furthermore, data from external quality assessment studies demonstrated that immunoassays methods for NT-proBNP share on average better analytical performances (including better sensitivity and imprecision) than those of BNP [1][2][3][4]. Furthermore, these studies also reported that there are large systematic differences (up to twofolds) between the BNP values measured by the most popular immunoassay methods, whereas the NT-proBNP methods show a between-method variability lower than 20% because they use calibrators and materials from the same manufacturer [3,4]. Finally, from a clinical point of view, the circulating levels of NT-proBNP show a greater and progressive increment (on average, more than 120-folds compared to healthy subjects) from early to more severe disease in patients with heart failure (HF), as assessed by NYHA functional class, than those of BNP (i.e.…”

“…On the other hand, there are large systematic differences (up to twofolds) between the commercial immunoassay methods so far available for BNP assay [45][46][47][48]. These differences are in part attributable to specific interferences related to the presence in clinical samples of proBNP and its degradation products [1,36,49].…”

“…These differences are in part attributable to specific interferences related to the presence in clinical samples of proBNP and its degradation products [1,36,49]. According to these evidences [1,36,[44][45][46][47][48][49], the commercially available immunoassay methods, considered specific for the active hormone BNP, present an obvious paradox. As discussed in the previous paragraph, BNP immunoassays should specifically measure only the active peptide hormone because clinicians could be interested in evaluating the "true biologically active status" of the cardiac endocrine function [1,14].…”