Effect of glycosoaminoglycans on the clinical course of diabetic nephropathy at the stage of microalbuminuria in patients with type 2 diabetes mellitus

Aim.
To evaluate clinical efficiency of sulodexide (glycosoaminoglycan) for the treatment of patients with type 2 diabetes mellitus (DM2) and diabeticnephropathy (DN) at the stage of microalbuminuria (MAU).
Materials and methods.
A total of 30 patients with DM2 and MAU were examined 15 of whom were given sulodexide (200 mg daily) for 6 months.The following parameters were measured before, 3 and 6 months after the onset of therapy: HbA_1c level, biochemical characteristics, highly sensitiveCRB, MAU in morning urine samples, soluble intercellular and vascular cell adhesion molecules-1, blood coagulation and anticoagulation factors(PTI, fibrinogen, thrombin time, coagulation factors VII, VIII, X, Willebrand factor), tissue plasminogen activator, and its inhibitor.
Results.
Sulodexide produced significant positive effect on albumin excretion in urine. It exerted antithromotic and profibrinolytic action and improvedendothelial function. Taken together, these properties of sulodexide give reason to recommend it as a protector of different vascular segments.
Conclusion.
Significant positive effect of sulodexide on albumin excretion in urine coupled to its multifactor activity, convenience of therapeutic application,low risk of complications, good tolerability, and safety in aged patients with DM2 permit to consider it as a promising tool for the treatmentof DM2 with MAU.

dibetes mellitus, diabetic nephropathy, microalbuminuria, heparin sulfate, sulodexide

1. Дедов И.И., Шестакова М.В. Диабетическая нефропатия. - М.: Уни- версум Паблишинг, 2000. - C. 114.

2. Yildirimtьrk O., Kilicgedik M., Tuğcu A., Aytekin V., Aytekin S. The relationship of microalbuminuria with left ventricular functions and silent myocardial ischemia in asymptomatic patients with type 2 diabetes // Arch. Turk. Soc. Cardiol. - 2009. - 37(2). - Р. 91-97.

3. Borch-Johnsen K., Feldt-Rasmussen B., Strandgaard S., Schroll M., Jensen J.S. Urinary albumin excretion. An independent predictor of ischemic heart disease // Arterioscler Thromb. Vasc. Biol. - 1999. - 19. - P. 1992-1997.

4. Dinneen S.F., Gerstein H.C. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature // Arch. Intern. Med. - 1997. - 157. - P. 1413-1418.

5. Wei-Wei Zhan, Yu-Hong Chen, Yi-Fei Zhang. Carotid stiffness and microalbuminuria in patients with type 2 diabetes // Endocrine. - 2009. - 35 - P. 409-413.

6. Aekplakorn W., Srivanichakorn S., Sangwatanaroj S. Microalbuminuria and metabolic risk factors in patients with type 2 diabetes in primary care setting in Thailand // Diabetes Res. Clin. Pract. - 2009. - 84(1). - P. 92-98.

7. Zhou J., Jia W.P., Ma X.J., Bao Y.Q., Lu W., Li M., Li Q., Hu C., Xiang K.S. Relationship between blood glucose variability and microalbuminuria in type 2 diabetic patients with well-controlled glycosylated hemoglobin // Article in Chinese. Zhonghua Yi Xue Za Zhi. - 2008. - 18(42). - P. 2977-2981.

8. Stehouwer C.D., Fischer H.R., van Kuijk A.W., Polak B.C., Donker A.J. Endothelial dysfunction precedes development of microalbuminuria in IDDM // Diabetes. - 1995. - 44. - P. 561-564.

9. Deckert T., Feldt-Rasmussen B., Borch-Johnsen K., Jensen T., Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis // Diabetologia. - 1989. - 32(4). - P. 219-226.

10. Amann K., Wanner C., Ritz E. Cross-talk between the kidney and the cardiovascular system // J. Am. Soc. Nephrol. - 2006. - 17. - P. 2112- 2119.

11. Satchell S., Anderson K., Mathieson P. Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties // J. Am. Soc. Nephrol. - 2004. - 15. - P. 566-574.

12. Jarad G., Miner J. Update on the glomerular filtration barrier // Curr. Opin. Nephrol. Hypertens. - 2009. - 18(3). - P. 226-232.

13. Pries A., Secomb T., Gaehtgens P. The endothelial surface layer // Pflugers. Arch. - 2000. - 440. - P. 653-666.

14. Salmon A., Neal C., Harper S. New aspects of glomerular filtration barrier structure and function: five layers (at least) not three // Curr. Opin. Nephrol. Hypertens. - 2009. - 18(3). - P. 197-205.

15. Satchell S., Tooke J. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? // Diabetologia. - 2008. - 51(5). - P. 714-772.

16. Max Nieuwdorp, Hans L. Mooij, Kroon J. Endothelial Glycocalyx Damage Coincides With Microalbuminuria in Type 1 Diabetes // Diabetes. - 2006. - 55. -P. 1127-1132.

17. Gambaro G., Kinalska I., Oksa A., Pont'uch P., Hertlovб M., Olsovsky J., Manitius J., Fedele D., Czekalski S., Perusicovб J., Skrha J., Taton J., Grzeszczak W., Crepaldi G. 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. - P. 1615-1625.

18. Singh A., Satchell S.C., Neal C.R., McKenzie E.A., Tooke J.E., Mathieson P.W. Glomerular Endothelial Glycocalyx Constitutes a Barrier to Protein Permeability // J. Am. Soc. Nephrol. - 2007. - 18. - P. 2885-2893.

19. Harvey S., Miner J. Revisiting the glomerular charge barrier in the molecular era // Curr. Opin. Nephrol. Hypertens. - 2008. - 17(4). - P. 393-398.

20. Miner J.H. Renal basement membrane components // Kidney. Int. - 1999. - 56. - P. 2016-2024.

21. Abaterusso C., Gambaro G. The role of glycosaminoglycans and sulodexide in the treatment of diabetic nephropathy // Treat. Endocrinol. - 2006. - 5(4). - P. 211-222.