Sulodexide: meta-analysis of the treatment of diabetic nephropathy and literature review

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Abstract

Objective. Discussion of the results of a meta-analysis that was conducted to evaluate the effectiveness of sulodexide treatment of diabetic nephropathy.

Results. Sulodexide is a heterogeneous group of sulfated glycosaminoglycans; which mainly consists of low molecular weight heparin. Clinical studies have shown that sulodexide is able to reduce urinary albumin excretion in patients with type 1 and type 2 diabetes mellitus (DM). A meta-analysis was conducted to summarize the clinical results of all prospective clinical studies on the clinical efficacy and safety of sulodexide in diabetic patients with nephropathy. In general; sulodexide therapy was accompanied by a significant decrease in urinary protein excretion. In the sulodexide group; 220 patients (17.7%) achieved a reduction in albumin excretion of at least 50% compared with 141 (11.5%) in the placebo group. The odds ratio in patients with therapeutic efficacy between the sulodexide and placebo groups was 3.28 (95% confidence interval: 1.34–8.06; P=0.01).

Conclusion. These data indicate the renoprotective effect of sulodexide in diabetic patients with microand macroalbuminuria and may be the basis for the treatment of diabetic nephropathy with sulodexide; in particular; the prevention of end-stage renal disease associated with DM [1].

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About the authors

Maria S. Novikova

Endocrinological Dispensary of the Moscow Healthcare Department; Central State Medical Academy of the Administrative Department of the President of the Russian Federation

Author for correspondence.
Email: citrus7474@mail.ru
ORCID iD: 0000-0003-1320-0565

Cand. Sci. (Med.), Associate Professor at the Department of Therapy; Cardiology and Functional Diagnostics with a Course in Nephrology, Nephrologist

Russian Federation, Moscow; Moscow

O. M. Koteshkova

Endocrinological Dispensary of the Moscow Healthcare Department

Email: citrus7474@mail.ru
Russian Federation, Moscow

M. B. Antsiferov

Endocrinological Dispensary of the Moscow Healthcare Department

Email: citrus7474@mail.ru
Russian Federation, Moscow

References

  1. Rui Li.; Jing Xing; Xaojing Mu; et al. Sulodexide therapy for the treatment of diabetic nephropathy; a meta-analysis and literature review. Drug Des Devel Ther. 2015;9:6275–83. doi: 10.2147/DDDT.S87973.
  2. Achour A.; Kacem M.; Dibej K.; et al.. One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2005;18(5):568–74.
  3. Ravera M.; Re M.; Weiss U.; et al. Emerging therapeutic strategies in diabetic nephropathy. J Nephrology. 2007;20(12):23–32.
  4. Reidy K.; Kang H.M.; Hostetter T.; Susztak K. Molecular mechanisms of diabetic kidney disease. J Clin Invest. 2014;124(6):2333–40. doi: 10.1172/JCI72271.
  5. Toth-Manikowski S.; Atta M.G. Diabetic kidney disease: pathophysiology and therapeutic targets. J Diabetes Res. 2015;2015:697010. doi: 10.1155/2015/697010.
  6. Valocikova I. Sulodexid and nephrotic syndrome in patients with diabetic nephropathy. Vnitr Lek. 2011;57(5):507–10.
  7. Шестакова М.В.; Чугунова Л.A.; Воронцов A.В.; Дедов И.И. Эффективность Сулодексида – низкомолекулярного гепарина – в терапии диабетической нефропатии. Терапевтический Архив. 1997;69(6):34–7. [Shestakova M.V.; Chugunova L.A.; Vorontsov A.V.; Dedov I.I. The effectiveness of Sulodexide low molecular weight heparin in the treatment of diabetic nephropathy. Terapevticheskiy Arkhiv. 1997;69(6):34–7. (In Russ.)].
  8. Lauver D.A.; Lucchesi B.R. Sulodexide: a renewed interest in this glycosaminoglycan. Cardiovasc Drug Rev. 2006;24(3–4):214–26. doi: 10.1111/j.1527-3466.2006.00214.x.
  9. Reeves W.B.; Rawal B.B.; Abdel-Rahman E.M.; Awad A.S. Therapeutic modalities in diabetic nephropathy: future approaches. Open J Nephrol. 2012;2(2):5–18. doi: 10.4236/ojneph.2012.22002.
  10. Залевская А.Г.; Астамирова Х.С.; Карпова И.А.; Попова С.Г. Испытание низкомолекулярного гепарина сулодексида в терапии диабетической нефропатии. Терапевтический Архив. 1998;70(3):71–4. [Zalevskaya A.G.; Astamirova Kh.S.; Karpova I.A.; Popova S.G. Testing of low molecular weight heparin sulodexide in the treatment of diabetic nephropathy. Terapevticheskiy Arkhiv. 1998;70(3):71–4. (In Russ.)].
  11. Skrha J.; Perusicova J.; Kvasnicka J.; Hilgertová J. The effect of glycosaminoglycan sulodexide on oxidative stress and fibrinolysis in diabetes mellitus. Sb Lek. 1998;99(2):103–9.
  12. Lewis E.J.; Lewis J.B.; Greene T.; et al. Collaborative Study Group Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: a randomized controlled trial. Am J Kidney Dis. 2011;58(5):729–36. doi: 10.1053/j.ajkd.2011.06.020.
  13. Packham D.K.; Wolfe R.; Reutens A.T.; et al. Collaborative Study Group Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy. J Am Soc Nephrol. 2012;23(1):123–30. doi: 10.1681/ASN.2011040378.
  14. Kunz R.; Friedrich C.; Wolbers M.; Mann J.F. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148(1):30–48. doi: 10.7326/0003-4819-148-1-200801010-00190.
  15. Friedrich J.O.; Adhikari N.; Herridge M.S.; Beyene J. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med. 2005;142(7):510–24. doi: 10.7326/0003-4819-142-7-200504050-00010.
  16. Poplawska A.; Szelachowska M.; Topolska J.; et al. Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with microor macroalbuminuria. Diabetes Res Clin Pract. 1997;38(2):109–14. doi: 10.1016/s0168-8227(97)00096-x.
  17. Skrha J.; Perusicova J.; Pont’uch P.; Oksa A. Glycosaminoglycan sulodexide decreases albuminuria in diabetic patients. Diabetes Res Clin Pract. 1997;38(1):25–31. doi: 10.1016/s0168-8227(97)00076-4.
  18. Blouza S.; Dakhli S.; Abid H.; et al. DAVET (Diabetic Albuminuria Vessel Tunisia Study Investigators) Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2010;23(4):415–24.
  19. Дедов И.И.; Шестакова М.В.; Воронцов А.В.; Палаццини Е. Рандомизированное контролируемое исследование терапии сулодексидом для лечения диабетической нефропатии. Nephrol Dial Transplant. 1997;12(11):2295–300. [Dedov I.I.; Shestakova M.V.; Vorontsov A.V.; Palazzini E. Randomized controlled trial of sulodexide therapy for the treatment of diabetic nephropathy. Nephrol Dial Transplant. 1997;12(11):2295–300. (In Russ.)].
  20. Sulikowska B.; Olejniczak H.; Muszyńska M.; et al. Effect of sulodexide on albuminuria; NAG excretion and glomerular filtration response to dopamine in diabetic patients. Am J Nephrol. 2006;26(6):621–28. doi: 10.1159/000098195.
  21. Kang Z. Study on effect of Sulodexide in treatment of diabetic nephropathy stage III. Guide of China Medicine. 2013;11:25–8.
  22. Heerspink H.L.; Greene T.; Lewis J.B.; et al. Collaborative Study Group Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria. Nephrol Dial Transplant. 2008;23(6):1946–54. doi: 10.1093/ndt/gfm893.
  23. Gambaro G.; Kinalska I.; Oksa A.; et al. Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.S. randomized trial. J Am Soc Nephrol. 2002;13(6):1615–25. doi: 10.1097/01.asn.0000014254.87188.e5.
  24. Gambaro G. Discounting the efficacy of sulodexide in diabetic nephropathy is premature. Am J Kidney Dis. 2012;60(1):169–70. doi: 10.1053/j.ajkd.2012.01.029.
  25. Wilson T.W. Dealing with Paucity of Data in Meta-Analysis of Binary Outcomes [doctoral thesis] Hong Kong: The Chinese University of Hong Hong; 2006. URL: http://www.hkcochrane.cuhk.edu.hk/thesis_final.pdf
  26. Friedrich J.O.; Adhikari N.K.; Beyene J. Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol. 2007;7:5. doi: 10.1186/1471-2288-7-5.
  27. Radbill B.; Murphy B.; LeRoith D. Rationale and strategies for early detection and management of diabetic kidney disease. Mayo Clin Proc. 2008;83(12):1373–81. doi: 10.1016/S0025-6196(11)60786-6.
  28. Rossing P. Diabetic nephropathy: worldwide epidemic and effects of current treatment on natural history. Curr Diab Rep. 2006;6(6):479–83. doi: 10.1007/s11892-006-0083-y.
  29. Sarafidis P.A.; Khosla N.; Bakris G.L. Antihypertensive therapy in the presence of proteinuria. Am J Kidney Dis. 2007;49(1):12–26. doi: 10.1053/j.ajkd.2006.10.014.
  30. Khosla N.; Bakris G. Lessons learned from recent hypertension trials about kidney disease. Clin J Am Soc Nephrol. 2006;1(2):229–235. doi: 10.2215/CJN.00840805.
  31. Ziyadeh F.N.; Sharma K. Overview: combating diabetic nephropathy. J Am Soc Nephrol. 2003;14(5):1355–57. doi: 10.1097/01.asn.0000065608.37756.58.
  32. Adler S.G.; Schwartz S.; Williams M.E.; et al. Phase 1 study of anti-CTGF monoclonal antibody in patients with diabetes and microalbuminuria. Clin J Am Soc Nephrol. 2010;5(8):1420–28. doi: 10.2215/CJN.09321209.
  33. Miner J.H. Glomerular filtration: the charge debate charges ahead. Kidney Int. 2008;74(3):259–61. doi: 10.1038/ki.2008.260.
  34. Gaddi A.V.; Cicero A.F.; Gambaro G. Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered. Int J Nephrol Renovasc Dis. 2010;3:99–105. doi: 10.2147/ijnrd.s5943.
  35. Parthasarathy N.; Spiro R.G. Effect of diabetes on the glycosaminoglycan component of the human glomerular basement membrane. Diabetes. 1982;31(8 Pt 1):738–41. doi: 10.2337/diab.31.8.738.
  36. Tanios B.Y.; Ziyadeh F.N. Emerging therapies for diabetic nephropathy patients: beyond blockade of the reninangiotensin system. Nephron Extra. 2012;2(1):278–82. doi: 10.1159/000343312.
  37. Shimomura H.; Spiro R.G. Studies on macromolecular components of human glomerular basement membrane and alterations in diabetes. Decreased levels of heparan sulfate proteoglycan and laminin. Diabetes. 1987;36(3):374–81. doi: 10.2337/diab.36.3.374.
  38. Solini A.; Vergnani L.; Ricci F.; Crepaldi G. Glycosaminoglycans delay the progression of nephropathy in NIDDM. Diabetes Care. 1997;20(5):819–23. doi: 10.2337/diacare.20.5.819.
  39. Masola V.; Zaza G.; Gambaro G. Sulodexide and glycosaminoglycans in the progression of renal disease. Nephrol Dial Transplant. 2014;29(suppl 1):74–9. doi: 10.1093/ndt/gft389.
  40. Weiss R.; Niecestro R.; Raz I. The role of sulodexide in the treatment of diabetic nephropathy. Drugs. 2007;67(18):2681–96. doi: 10.2165/00003495-200767180-00004.
  41. Abaterusso C.; Gambaro G. The role of glycosaminoglycans and sulodexide in the treatment of diabetic nephropathy. Treat Endocrinol. 2006;5(4):211–22. doi: 10.2165/00024677-200605040-00002.
  42. Wijnhoven T.; Lensen J.F.; Rops A.L.; et al. Antiproteinuric effects of glycosaminoglycan-based drugs. Curr Opin Mol Ther. 2007;9(4):364–77.
  43. House A.A.; Weir M.A. Sulodexide for diabetic nephropathy: another one bites the dust. Am J Kidney Dis. 2011;58(5):692–94. doi: 10.1053/j.ajkd.2011.08.011.
  44. Coccheri S. Game not over for sulodexide. Am J Kidney Dis. 2012;59(3):467. doi: 10.1053/j.ajkd.2011.12.010.
  45. Yung S.; Chau M.K.; Zhang Q.; et al. Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy. PLoS One. 2013;8(1):e54501. Yung S.; Chau M.K.; Zhang Q.; et al. Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy. PLoS One. 2013;8(1):e54501.
  46. Masola V.; Onisto M.; Zaza G.; et al. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J Transl Med. 2012;10:213. doi: 10.1186/1479-5876-10-213.
  47. Cha J.J.; Kang Y.S.; Hyun Y.Y.; et al. Sulodexide improves renal function through reduction of vascular endothelial growth factor in type 2 diabetic rats. Life Sci. 2013;92(23):1118–24. doi: 10.1016/j.lfs.2013.04.008.
  48. Kristova V.; Liskova S.; Sotnikova R.; et al. Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res. 2008;57(3):491–94. doi: 10.33549/physiolres.931506.
  49. Coccheri S.; Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Devel Ther. 2014;8:49–65. doi: 10.2147/DDDT.S6762
  50. Lambers Heerspink H.J.; Fowler M.J.; Volgi J.; et al. Collaborative Study Group Rationale for and study design of the sulodexide trials in Type 2 diabetic; hypertensive patients with microalbuminuria or overt nephropathy. Diabet Med. 2007;24(11):1290–95. doi: 10.1111/j.1464-5491.2007.02249.x.
  51. Bu H.; Xu K.; Zhang H. The effect of sulodexide on the diabetic nephropathy. Journal of Henan Medical College for Staff and Workers. 2012;24(2):146–47.
  52. Liu S. Therapeutic effects of sulodexide combined with benazapril on patients with diabetic kidney disease. Chin J Diffic and Compl Cas. 2011;10:21–2.
  53. Xiong Y. Treatment of sulodexide on albuminuria in early diabetic nephropathy. J Jianghan Univ (Nat Sci Ed) 2014;42:90–2.

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