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The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure
  1. Toshio Nishikimi1,2,
  2. Masashi Ikeda3,
  3. Yosuke Takeda2,
  4. Toshihiko Ishimitsu2,
  5. Ikuko Shibasaki4,
  6. Hirotsugu Fukuda4,
  7. Hideyuki Kinoshita1,
  8. Yasuaki Nakagawa1,
  9. Koichiro Kuwahara1,
  10. Kazuwa Nakao1
  1. 1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan
  3. 3Institute of International Education and Research, Dokkyo Medical University, Mibu, Tochigi, Japan
  4. 4Department of Cardiovascular Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan
  1. Correspondence to Professor Toshio Nishikimi, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54, Shogoin-Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan; nishikim{at}kuhp.kyoto-u.ac.jp

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.

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Footnotes

  • Funding This study was supported in part by Scientific Research Grants-in-Aid 18590787 and 20590837 from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the ethics committee of the authors' institute and was carried out in accordance with the recommendations of the ethical committee of Dokkyo Medical University.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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