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

• Confirmed HBV-MN is a kidney disease associated with complement activation.
• Sulodexide could inhibit the activation of complement system.
• Anti-virus therapy might not obviously affect activation of complement system.
• Two agents could both improve the prognosis of the patients with HBV-MN.

BackgroundThe 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.MethodsThis 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 0.5 mg entecavir plus 150–300 mg/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 1 year (Group 2), 500 lsu/day for 1 year (Group 3) and 1000 lsu/day for 6 months followed by 250 lsu/day for 6 months (Group 4). Major clinical outcomes were valid remission (VR): (1) urine albumin/creatinine ratio (UACR) < 150 mg/mmol and > 50% decline of baseline; (2) albumin > 35 g/L; (3) glomerular filtration rate (GFR) > 90 ml/(min*1.73m2).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.