TITLE:
A Mixture of Glycosylated proBNP and BNP-32 Is a Suitable Calibrator for BNP Immunoassays
AUTHORS:
Keiichi Masuta, Kenzo Funatsuki, Youko Inoue, Izuru Masuda, Toshio Nishikimi, Yasuaki Nakagawa, Kazukiyo Horii, Hiroshi Nishi, Masayo Igarashi, Norio Ota
KEYWORDS:
B-Type Natriuretic Peptide (BNP), proBNP, Calibrator
JOURNAL NAME:
Open Journal of Clinical Diagnostics,
Vol.9 No.2,
June
29,
2019
ABSTRACT: Aim: Measurement of B-type natriuretic peptide (BNP) is widely used as a
diagnostic and risk assessment tool for cardiovascular disease. Recent studies
have demonstrated that BNP-32 and its precursor proBNP circulate in the blood stream, and that most commercial BNP immunoassays
measure both forms. However, recombinant or synthetic BNP-32 is used as the
standard for those BNP immunoassays. This gap between clinical samples and the
standard might be a potential source of variation in BNP measurements among
assays. The purpose of this study is to validate a more suitable calibrator for
BNP immunoassays. Methods: External BNP calibrators containing both BNP-32 and glycosylated proBNP
were prepared at two concentration levels. Target BNP concentrations of the low
and high levels were 40 and 160 pg/mL, respectively. And to reflect clinical
samples, the molar ratios of BNP-32 to glycosylated proBNP in these
concentration levels were adjusted to 50:50 and 25:75, respectively. BNP
concentrations of plasma samples along with the external BNP calibrators were
measured at two commercial labs and using an automated analyzer MI02 Shionogi® BNP
(MI02). These samples and the calibrators were also measured using an
immunoradiometric assay (IRMA) as a standard assay procedure. Concentrations of
the plasma samples measured at the labs or using the MI02 were adjusted
according to a comparison of the measured concentrations of the external BNP
calibrators with the IRMA. Results: After measured concentrations of the plasma samples were adjusted using
the external BNP calibrators, the correlation between each measurement and the
IRMA was improved. The range of the slopes according to Passing-Bablok
regression analysis narrowed from 0.628 - 0.955 to
0.911 - 1.005. Conclusions: Our data
suggests that a
mixture of BNP-32 and glycosylated proBNP at different ratios by concentration
level is suitable for calibration to minimize variations in BNP measurements
among immunoassays.