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

  • Author Footnotes
    1 These authors contributed as much to the work as the first author.
    Yang Yang
    Footnotes
    1 These authors contributed as much to the work as the first author.
    Affiliations
    Kidney Institute of PLA, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

    Kidney Therapeutic Center of Traditional Chinese and Western Medicine, Beidaihe Sanatorium of Beijing Military Region, Qinhuangdao, China
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  • Author Footnotes
    1 These authors contributed as much to the work as the first author.
    Lu Ma
    Footnotes
    1 These authors contributed as much to the work as the first author.
    Affiliations
    Kidney Therapeutic Center of Traditional Chinese and Western Medicine, Beidaihe Sanatorium of Beijing Military Region, Qinhuangdao, China
    Search for articles by this author
  • Chao Wang
    Affiliations
    Kidney Therapeutic Center of Traditional Chinese and Western Medicine, Beidaihe Sanatorium of Beijing Military Region, Qinhuangdao, China
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  • Deyang Kong
    Affiliations
    Department of Nephrology, First Affiliated Hospital of Haerbin Medical University, Haerbin, China
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  • YaPing Wang
    Affiliations
    Department of Nephrology, General Hospital of Beijing Military Region, Beijing, China
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  • Changlin Mei
    Correspondence
    Corresponding author at: Fengyang Road, No. 415, Huangpu District (+86+200003), Shanghai, China. Tel.: +86 21 81870763.
    Affiliations
    Kidney Institute of PLA, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed as much to the work as the first author.

      Highlights

      • 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.

      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 0.5 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.

      Keywords

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