The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure. Issue 2 (30th June 2011)

• Record Type: Journal Article
• Authors: Nishikimi, Toshio; Ikeda, Masashi; Takeda, Yosuke; Ishimitsu, Toshihiko; Shibasaki, Ikuko; Fukuda, Hirotsugu; Kinoshita, Hideyuki; Nakagawa, Yasuaki; Kuwahara, Koichiro; Nakao, Kazuwa
• Is Part Of: Heart. Volume 98:Issue 2(2012)
• Page Start: 152
• Page End: 161
• Publication Date: 2011-06-30
• Subjects: N-Terminal-proBNP -- glycosylation -- cardiac hormones -- heart failure -- chronic renal failure -- acute myocardial infarction -- hypertension—renal -- adrenomedullin -- chronic heart failure -- neurohormones -- atrial natriuretic peptide -- natriuretic peptides -- heart failure treatment -- heart failure -- hypertrophy -- cardiac remodelling -- growth factors; Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2011-300102
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Objective: Pro-brain natriuretic peptide (proBNP)-108 and N-terminal proBNP-76 (NT-BNP) contain seven sites for O -linked oligosaccharide attachment. Currently, levels of glycosylated NT-BNP are probably underestimated because it is not recognised by one antibody in the sandwich assay system. The pathophysiological significance of cardiac and plasma levels of non-glycosylated (nonglyNT-BNP) and glycosylated NT-BNP (glyNT-BNP) in heart failure (HF) and chronic renal failure (CRF) was investigated. Methods: Plasma samples from 186 patients with HF and 76 patients with CRF on haemodialysis were studied, together with 11 atrial tissue samples. To measure nonglyNT-BNP and glyNT-BNP, samples were incubated with or without deglycosylating enzymes and NT-BNP was measured using Roche Elecsys proBNP I. The percentage glyNT-BNP was calculated as glyNT-BNP/(glyNT-BNP + nonglyNT-BNP). Results: In HF, plasma BNP, nonglyNT-BNP and glyNT-BNP levels all increased with increasing disease severity (New York Heart Association class; p<0.0001), though the molar ratio remained constant (molar ratio, BNP:nonglyNT-BNP:glyNT-BNP = 1:2.4:9.6). Before haemodialysis for CRF, plasma BNP and nonglyNT-BNP were somewhat elevated, and glyNT-BNP was markedly increased (molar ratio, BNP:nonglyNT-BNP:glyNT-BNP = 1:8.5:82). After haemodialysis, plasma BNP, nonglyNT-BNP, atrial natriuretic protein and cGMP all declined (p<0.0001), but glyNT-BNP was unchanged. Notably, the percentage of glyNT-BNP was elevated before haemodialysis, and was further increased after haemodialysis (p<0.0001). Atrial tissue levels of BNP, nonglyNT-BNP and glyNT-BNP were similar. Conclusion: The findings suggest that most endogenous plasma NT-BNP is glycosylated and therefore undetectable with the current assay system, and that the relative glycosylation level is increased by haemodialysis.