title: The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara-cho, Sakyo-ku, Kyoto, Japan. nishikim@kuhp.kyoto-u.ac.jp
authors: Toshio
authors: T
authors: Nishikimi
authors: Masashi
authors: M
authors: Ikeda
authors: Yosuke
authors: Y
authors: Takeda
authors: Toshihiko
authors: T
authors: Ishimitsu
authors: Ikuko
authors: I
authors: Shibasaki
authors: Hirotsugu
authors: H
authors: Fukuda
authors: Hideyuki
authors: H
authors: Kinoshita
authors: Yasuaki
authors: Y
authors: Nakagawa
authors: Koichiro
authors: K
authors: Kuwahara
authors: Kazuwa
authors: K
authors: Nakao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006031:Glycosylation; D006333:Heart Failure / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood* / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain