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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References
- Hepatitis B virus infection.Lancet. 2009; 373: 582-592
- Update on epidemiology of hepatitis B and C in China.J Gastroenterol Hepatol. 2013; 28: 7-10
- Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations.Kidney Int. 1990; 37: 663-676
- Hepatitis B virus-associated nephropathy.Am J Nephrol. 2004; 24: 198-211
- Heparin/heparan sulphate interactions with complement—a possible target for reduction of renal function loss?.Nephrol Dial Transplant. 2014; 29: 515-522
- Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria.Nephrol Dial Transplant. 2008; 23: 1946-1954
- Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: a randomized controlled trial.Am J Kidney Dis. 2011; 58: 729-736
- Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.J Am Soc Nephrol. 2006; 17: 2937-2944
- Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update.Hepatol Int. 2008; 2: 263-283
- Transient elastography: a new noninvasive method for assessment of hepatic fibrosis.Ultrasound Med Biol. 2003; 29: 1705-1713
- Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults.Kidney Int Suppl. 1991; 35: S40-S45
- Membranous nephropathy related to hepatitis B virus in adults.N Engl J Med. 1991; 324: 1457-1463
- Viral infections and the kidney: HIV, hepatitis B, and hepatitis C.Cleve Clin J Med. 2007; 74: 353-360
- Prophylaxis of thromboembolic events in patients with nephrotic syndrome.Ann Pharmacother. 2013; 47: 725-734
- Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection.Gastroenterology. 2002; 123: 1831-1838
- Treatment of hepatitis B virus-associated nephropathy.Nephron Clin Pract. 2011; 119 ([discussion c9]): c41-c49
- Seroconversion of hepatitis B envelope antigen by entecavir in a child with hepatitis B virus-related membranous nephropathy.J Nippon Med Sch. 2013; 80: 387-395
- Clinical and pathological analysis of hepatitis B virus-related membranous nephropathy and idiopathic membranous nephropathy.Clin Nephrol. 2012; 78: 456-464
- Kinetic studies on the interactions of heparin and complement proteins using surface plasmon resonance.Biochim Biophys Acta. 1726; 2005: 168-176
- Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects.Int Angiol. 2014; 33: 243-254
- Specific complement inhibition with heparin-coated extracorporeal circuits.Ann Thorac Surg. 1996; 61: 1153-1157
- Low-molecular-weight heparin inhibition in classical complement activation pathway during pregnancy.Thromb Res. 2010; 125: e240-e245
- In vivo antithrombotic synergy of oral heparin and arginine: endothelial thromboresistance without changes in coagulation parameters.Thromb Haemost. 2006; 95: 865-872
- New approaches to the treatment of dense deposit disease.J Am Soc Nephrol. 2007; 18: 2447-2456
- Anti-proteinuric effect of sulodexide in immunoglobulin a nephropathy.Yonsei Med J. 2011; 52: 588-594
- Heparan sulfate–rich anionic sites in the human glomerular basement membrane. Decreased concentration in congenital nephrotic syndrome.N Engl J Med. 1983; 309: 1001-1009
- Glomerular anionic sites in minimal change nephrotic syndrome and focal segmental glomerulosclerosis.Clin Nephrol. 1993; 40: 199-204
- Steroid-responsive nephrotic syndrome: a generalised disorder of membrane negative charge.Lancet. 1985; 2: 239-242
- Glycosaminoglycan excretion in children with nephrotic syndrome.Pediatr Nephrol. 2005; 20: 486-490
- Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure.Acta Pharmacol Sin. 2012; 33: 644-651
- The role of sulodexide in the treatment of diabetic nephropathy.Drugs. 2007; 67: 2681-2696
- Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy.J Am Soc Nephrol. 2012; 23: 123-130
Article info
Publication history
Published online: May 05, 2016
Accepted:
April 15,
2016
Received in revised form:
April 5,
2016
Received:
December 9,
2015
Footnotes
☆All authors declared no conflicts of interest for this article.
Identification
Copyright
© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
