Effectiveness of sulodexide might be associated with inhibition of complement system in hepatitis B virus-associated membranous nephropathy: An inspiration from a pilot trial

Eur J Intern Med. 2016 Jul:32:96-104. doi: 10.1016/j.ejim.2016.04.017. Epub 2016 May 6.

Abstract

Background: The activation of complement system is associated with the development of hepatitis B virus-associated membranous nephropathy (HBV-MN) and heparin could inhibit the activation of complement system.

Methods: This was a three-center trial. Seventy-nine patients with HBV-MN participated in the study. The follow-up of the study consisted of two periods: Stage 1 (S1) and Stage 2 (S2). All patients received 0.5mg entecavir plus 150-300mg/day of irbesartan but sulodexide was prescribed during S1. They were randomized into 4 groups according to sulodexide dose: blank (Group 1), 250 lipasemic unit (lsu)/day for 1year (Group 2), 500 lsu/day for 1year (Group 3) and 1000 lsu/day for 6months followed by 250 lsu/day for 6months (Group 4). Major clinical outcomes were valid remission (VR): (1) urine albumin/creatinine ratio (UACR) <150mg/mmol and >50% decline of baseline; (2) albumin >35g/L; (3) glomerular filtration rate (GFR) >90ml/(min*1.73m(2)).

Results: (1) Groups 3 and 4 had significantly lower UACR and higher albumin than did Groups 1 and 2 at major visits; (2) Groups 3 and 4 achieved more VR compared with Group 1 (42.1% and 60.0% vs. 9.1%, p both<0.05); (3) in Groups 3 and 4, instead of Groups 1 and 2, more C3 deposition in the kidney was observed in those achieving VR; (4) plasma C3a, C5a and C5b-9 decreased significantly in Groups 3 and 4 during S1.

Conclusions: (1) The prescription of both sulodexide and entecavir could improve the prognosis of patients with HBV-MN but their mechanisms might be different; (2) the renoprotection of sulodexide in HBV-MN might probably relate to the inhibition of complement system.

Keywords: Anti-virus therapy; Complement; Glycosaminoglycan; Hepatitis B virus; Membranous nephropathy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anticoagulants / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Biphenyl Compounds / therapeutic use*
  • Complement System Proteins / immunology
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / etiology
  • Glomerulonephritis, Membranous / immunology
  • Glomerulonephritis, Membranous / virology
  • Glycosaminoglycans / therapeutic use*
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B / complications
  • Hepatitis B / drug therapy*
  • Hepatitis B virus
  • Humans
  • Irbesartan
  • Male
  • Middle Aged
  • Pilot Projects
  • Tetrazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Anticoagulants
  • Antihypertensive Agents
  • Antiviral Agents
  • Biphenyl Compounds
  • Glycosaminoglycans
  • Tetrazoles
  • entecavir
  • Guanine
  • glucuronyl glucosamine glycan sulfate
  • Complement System Proteins
  • Irbesartan