Inhibitory effect of FUT-175 on complement activation and its application for glomerulonephritis with hypocomplementemia

Yoshiro Fujita, Itaru Inoue, Toshio Miyata, Takahiro Shinzato, Satoshi Sugiyama, Kenji Maeda, Reiko Inagi, Akio Miyama

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

FUT-175 (6-amidino-2-naphthyl p-guanidinobenzoate dimethane-sulphonate), a potent serine protease inhibitor, has been reported to inhibit complement activity in vitro, and especially the classical complement pathway effectively. In the present study, we examined the inhibitory effect of FUT-175 on the classical complement pathway components by hemolytic assay using purified human complement components. As a result, 50% inhibition of the Cl protease activity for classical C3 convertase formation and for C2 was obtained with 3.0˟10-8 M and 7.0˟10-8 M of FUT-175, respectively. FUT-175 did not inhibit the C2 protease activity at all. We then administered FUT-175 to 5 glomerulonephritic patients with hypocomplementemia and proteinuria in order to assess the clinical effectiveness of this drug. When FUT-175 was administered intravenously and continuously at a rate of 0.1 to 0.2 mg/kg/hr for 2 weeks, the urinary protein excretion decreased significantly from 2.9±0.8 to 1.4±0;5 g/day (P<0.025). In these patients, some of the serum complement markers (serum C3, C4 level and the hemolytic activity via the classical complement pathway (CH50)) were increased after FUT-175 administration. The above findings suggests that FUT-175 can exert beneficial effects on glomerulonephritis with hypocomplementemia by inhibiting complement activation.

Original languageEnglish
Pages (from-to)393-397
Number of pages5
JournalThe Japanese Journal Of Nephrology
Volume35
Issue number4
DOIs
Publication statusPublished - 1994 Jan 1
Externally publishedYes

Keywords

  • FUT-175
  • complement activation
  • glomerulonephritis
  • hypocomplementemia
  • serine protease inhibitor

ASJC Scopus subject areas

  • Nephrology

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