nach oben

Drugs

Erschienen in:

01.12.2007 | Review Article

The Role of Sulodexide in the Treatment of Diabetic Nephropathy

verfasst von: Dr Ram Weiss, Robert Niecestro, Itamar Raz

Erschienen in: Drugs | Ausgabe 18/2007

Einloggen, um Zugang zu erhalten

Abstract

Diabetic nephropathy is an important cause of morbidity and mortality in patients with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural history of diabetic nephropathy, characterised by a progressive decline in glomerular function, were initially described in patients with type 1 diabetes. Reports that describe the glomerulopathy and progression of renal disease in patients with type 2 diabetes suggest that the disease process is similar to that observed in patients with type 1 diabetes with diabetic nephropathy. An emerging body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve pathobiochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic, reveal that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Clinical reports of the use of sulodexide, a preparation of low molecular weight glycosaminoglycan polysaccharides, have shown that proteinuria is significantly diminished in patients with diabetic nephropathy, even when these patients are receiving either an ACE inhibitor or angiotensin receptor antagonist.

American Diabetes Association. Diabetic nephropathy. Diabetes Care 1998; 21: S50–3

United States Renal Data System. USRDS 1999 annual data report. Bethesda (MD): National Institute of Health, National Institute of Diabetes, Digestive, and Kidney Diseases, 1999: 25–164

Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 1999; 341: 1127–32PubMedCrossRef

Wight JP, Edwards L, Brazier J, et al. The SF36 as an outcome measure of services for end stage renal failure. Qual Health Care 1998; 7: 209–21PubMedCrossRef

Arkouche W, Traeger J, Delawari E, et al. Twenty-five years of experience with out-center hemodialysis. Kidney Int 1999; 56: 2269–75PubMedCrossRef

Johnson JG, Gore SM, Firth J. The effect of age, diabetes, and other comorbidity on the survival of patients on dialysis: a systematic quantitative overview of the literature. Nephrol Dial Transplant 1999; 14: 2156–64PubMedCrossRef

Remuzzi G, Schieppati A, Ruggenenti P. Nephropathy in patients with type 2 diabetes. N Engl J Med 2000; 346: 1145–51CrossRef

Wolf G, Ritz E. Diabetic nephropathy in type 2 diabetes prevention and patient management. J Am Soc Nephrol 2003; 14: 1396–405PubMedCrossRef

Fioretta P, Mauer M, Broco E, et al. Pattern of renal injury in NIDDM patients with microalbuminuria. Diabetologia 1996; 39: 1569–76CrossRef

10.

Bertani T, Gambara V, Remuzzi G. Structrual basis of diabetic nephropathy in microalbuminuric NIDDM patients: a light microscopy study. Diabetologia 1996; 39: 1625–8PubMedCrossRef

11.

Biesenbach G, Grafinger P, Janko O, et al. Influence of cigarette-smoking on the progression of clinical diabetic nephropathy in type 2 diabetic patients. Clin Nephrol 1997; 48: 146–50PubMed

12.

Ravid M, Brosh D, Levi Z, et al. Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus:a randomized, controlled trial. Ann Intern Med 1998; 128: 982–8PubMed

13.

Fioretto P, Steffes MW, Mauer M. Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria. Diabetes 1994; 43: 1358–64PubMedCrossRef

14.

Jensen T. Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan. Diabetes 1997; 46 Suppl. 2: S98–100PubMed

15.

Raats CJI, van den Born J, Berden JHM. Glomerular heparan sulfate alterations: mechanisms and relevance for proteinuria. Kidney Int 2000; 57: 385–400PubMedCrossRef

16.

van den Hoven M, Rops A, Bakker M. Increased expression of heparanase in overt diabetic nephropathy. Kidney Int 2006; 70: 2100–8PubMed

17.

Mauer SM, Lane P, Hattori M, et al. Renal structure and function in insulin-dependent diabetes mellitus and type I membranoproliferative glomerulonephritis in humans. J Am Soc Nephrol 1992; 2: S181–4PubMed

18.

Steffes MW, Bilous RW, Sutherland DE, et al. Cell and matrix components of the glomerular mesangium in type 1 diabetes. Diabetes 1992; 41: 679–84PubMedCrossRef

19.

Lei J, Silbiger S, Ziyadeh FN, et al. Serum-stimulated al type IV collagen gene transcription is mediated by TGF-β and inhibited by estradiol. Am J Physiol 1997; 274: F252–8

20.

Oh JH, Ha H, Yu MR, et al. Sequential effects of high glucose on mesangial cell transforming growth factor-β1 and fibronectin synthesis. Kidney Int 1998; 54: 1872–8PubMedCrossRef

21.

Ellis EN, Steffes MW, Goetz FC, et al. Glomerular filtration surface in type 1 diabetes mellitus. Kidney Int 1986; 29: 889–94PubMedCrossRef

22.

Eddy AA. Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol 1996; 7: 2495–508PubMed

23.

Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med 1998; 339: 1448–56PubMedCrossRef

24.

Bader R, Bader H, Grund KE, et al. Structure and function of the kidney in diabetic glomerulosclerosis: correlations between morphological and functional parameters. Path Res Pract 1980; 167: 204–16PubMedCrossRef

25.

Bohle A, Wehrmann M, Bogenschntz O, et al. The pathogenesis of chronic renal failure in diabetic nephropathy: investigation of 488 cases of diabetic glomerulosclerosis. Path Res Pract 1991; 187: 251–9PubMedCrossRef

26.

Taft JL, Nolan CJ, Yeung SP, et al. Clinical and histological correlations of decline in renal function in diabetic patients with proteinuria. Diabetes 1994; 43: 1046–51PubMedCrossRef

27.

Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease with emphasis on the stage of incipient diabetic nephropathy. Diabetes 1983; 32: 64–78PubMed

28.

Inomata S, Nakamoto Y, Inoue M, et al. Relationship between urinary albumin excretion rate and renal histology in non-insulin-dependent diabetes mellitus: with reference to the clinical significance of microalbuminuria. J Diabet Complications 1989; 3: 172–8PubMedCrossRef

29.

Pedrini MT, Levey AS, Lau J, et al. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med 1996; 124: 627–32PubMed

30.

The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86CrossRef

31.

United Kingdom Prospective Diabetes Study (UKPDS) Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998; 317: 713–20CrossRef

32.

Feldt-Rasmussen B, Mathiesen ER, Hegedns L, et al. Kidney function during 12 months of strict metabolic control in insulin-dependent diabetic patients with incipient nephropathy. N Engl J Med 1986; 314: 665–70PubMedCrossRef

33.

Parving HH. Renoprotective action of angiotensin converting enzyme inhibition in diabetes mellitus. J Cardiovasc Pharmacol 1992; 19 Suppl. 6: S19–24PubMedCrossRef

34.

Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–62PubMedCrossRef

35.

Parving HH, Smidt UM, Hommel E, et al. Effective antihyper-tensive treatment postpones renal insufficiency in diabetic nephropathy. Am J Kidney Dis 1993; 22: 188–95PubMed

36.

Parving H, Rossing P, Hommel E, et al. Angiotensin-converting enzyme inhibition in diabetic nephropathy: ten years’ experience. Am J Kidney Dis 1995; 26: 99–107PubMedCrossRef

37.

Rossing P, Hommel E, Smidt UM, et al. Reduction in albuminuria predicts diminished progression in diabetic nephropathy. Kidney Int 1994; 45 Suppl. 45: S145–9

38.

Jerums G. Differences in renal outcomes with ACE inhibitors in type 1 and type 2 diabetic patients: possible explanations. Miner Electrolyte Metab 1998; 24: 423–37PubMedCrossRef

39.

Lebovitz HE, Wiegmann TB, Cnaan A, et al. Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria. Kidney Int 1994; 45 Suppl. 45: S150–5

40.

Nielsen FS, Rossing P, Gall M, et al. Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes 1997; 46: 1182–8PubMedCrossRef

41.

Morelli E, Loon N, Meyer T, et al. Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy. Diabetes 1990; 39: 76–82PubMedCrossRef

42.

Ruggenenti P, Gambara V, Perna A, et al. The nephropathy of non-insulin-dependent diabetes: predictors of outcome relative to diverse patterns of renal injury. J Am Soc Nephrol 1998; 9: 2336–43PubMed

43.

Ruggenenti P, Remuzzi G. Nephropathy in type-2 diabetes mellitus. J Am Soc Nephrol 1998; 9: 2157–69PubMed

44.

Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 34(12): 861–9CrossRef

45.

Lewis EJ, Hunsicker LG, Clarke WR, et al. Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345(12): 851–60

46.

US FDA. Statistical review and evaluation: COZAAR (losartan potassium) tablets [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/02/briefing/3849bl_04_Statistical%20review.pdf [Accessed 2007 Sep 17]

47.

Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the losartan intervention for end-point reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 995–1003PubMedCrossRef

48.

Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effects of irbesartan on the development of diabetic nephropathy in patients with type diabetes. N Engl J Med 2001; 345: 870–8PubMedCrossRef

49.

Ruggenenti P, Fassi A, Ilieva AP, et al. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004; 351: 1941–51PubMedCrossRef

50.

Gambaro G, Van Der Woude FJ. Glycosaminoglycans: use in treatment of diabetic nephropathy. J Am Soc Nephrol 2000; 11: 359–68PubMed

51.

Gambaro G, Cavazzana AO, Luzi P, et al. Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats. Kidney Int 1992; 42: 285–91PubMedCrossRef

52.

Gambaro G, Venturini AP, Noonan DM, et al. Treatment with glycosaminoglycan formulation ameliorates experimental diabetic nephropathy. Kidney Int 1994; 46: 797–806PubMedCrossRef

53.

Ofosu FA. Pharmacological actions of sulodexide. Semin Thromb Hemost 1998; 24(2): 127–38PubMedCrossRef

54.

Nader HB, Buonassisi V, Colburn P, et al. Heparin stimulates the synthesis and modifies the sulfation pattern of heparan sulfate proteoglycan from endothelial cells. J Cell Physiol 1989; 40(2): 305–10CrossRef

55.

Xu X, Rao G, Maxihimer JB, et al. Mechanism of action of sulodexide-mediated control of diabetic proteinuria: inhibition of heparanase-1 activity [abstract]. J Am Soc Nephrol 2005; 16: 673ACrossRef

56.

Caenazzo C, Garbisa S, Ceol M, et al. Heparin modulates proliferation and proteoglycan biosynthesis in murine mesangial cells: molecular clues for its activity in nephropathy. Nephrol Dial Transplant 1995; 10(2): 175–84PubMed

57.

Caenazzo C, Garbisa S, Onisto M, et al. Effect of glucose and heparin on mesangial αl (IV) COLL and MMP-2/TIMP-2 mRNA expression. Nephrol Dial Transplant 1997; 12(3): 443–8PubMedCrossRef

58.

Oturai P, Rolin B, Vissing H. Effects of heparin on kidney TGF-β1 mRNA in experimental diabetic nephropathy [abstract]. Diabetes 1997; 46: 120A

59.

Wang ZQ, Liang KH, Pahl MV, et al. Effect of heparin on mesangial cell growth and gene expression of matrix proteins. Nephrol Dial Transplant 1998; 13: 3052–7PubMedCrossRef

60.

Yokokawa K, Kohno M, Mandal AK, et al. Heparin suppresses endothelin-1 (ET-1) peptide and mRNA expression in cultured endothelial cells of spontaneously hypertensive rats. J Am Soc Nephrol 1994; 4: 1683–9PubMed

61.

Reantragoon S, Arrigo LM, Seoud MMA, et al. Specific heparin fractions suppress ET-1 production in cultured human umbilical vein endothelial cells. Arch Biochem Biophys 1994; 314: 315–22PubMedCrossRef

62.

Zoja C, Morigi M, Figliuzzi M, et al. Proximal tubular cell synthesis and secretion of ET-1 on challenge with albumin and other proteins. Am J Kid Dis 1995; 26: 934–41PubMedCrossRef

63.

Piatti PM, Monti LD, Valsecchi G, et al. Effects of low-dose heparin infusion on arterial ET-1 release in humans. Circulation 1996; 94: 2703–7PubMedCrossRef

64.

Valencia AO, Mileva MM, Dweck HS, et al. Specificity of glycosaminoglycan suppression of ET-1 production by human umbilical vein endothelial cells. Life Sci 1999; 65(3): 279–84PubMedCrossRef

65.

Matsumoto T, Yamaguchi M, Kikuchi H, et al. Heparin reduces serum levels of ET-1 and hepatic ischemia reperfusion injury in rabbits. Surg Today 2000; 30(6): 523–5PubMedCrossRef

66.

Mizutani K, Kawashima S, Ueyama T, et al. Heparin and heparan sulfate inhibit extracellular signal-regulated kinase activation and myocardial cell hypertrophy induced by endothelin-1. Kobe J Med Sci 2001; 47(2): 47–58PubMed

67.

Ishikawa Y, Kitamura M. Inhibition of glomerular cell apoptosis by heparin. Kidney Int 1999; 56(3): 954–63PubMedCrossRef

68.

Tiozzo R, Cingi MR, Pietrangelo A, et al. Effect of heparin-like compounds on the in vitro proliferation and protein synthesis of various cell types. Arzneimittel-Forschung / Drug Research 1989; 39: 15–20

69.

Barbanti M, Guizzardi S, Calanni F, et al. Antithrombotic and thrombolytic activity of sulodexide in rats. Int J Clin Lab Res 1992; 22: 179–84PubMedCrossRef

70.

Buchanan MR, Liao P, Smith LJ, et al. Prevention of thrombus formation and growth by antithrombin III and heparin cofactor II-dependent thrombin inhibitors: importance of heparin cofactor II. Thromb Res 1994; 74(5): 463–75PubMedCrossRef

71.

Lauver DA, Lucchesi BR. Sulodexide: a renewed interest in this glycosaminoglycan. Cardiovasc Drug Rev 2006; 24: 214–26PubMedCrossRef

72.

Lauver DA, Booth EA, White AJ, et al. Sulodexide attenuates myocardial ischemia/reperfusion injury and the deposition of c-reactive protein in areas of infarction without affecting hemostatic. J Pharmacol Exp Ther 2005; 312: 794–800PubMedCrossRef

73.

Crepaldi G, Fellin R, Calabro A, et al. Preliminary results of sulodexide treatment in patients with peripheral arteriosclerosis and hyperlipemia: a multicentre trial. Monogr Atheroscler 1986; 14: 215–21PubMed

74.

Radhakrishnamurthy B, Sharma C, Bhandara RR, et al. Studies of chemical and biologic properties of a fraction of sulodexide, a heparin-like glycosaminoglycan. Atherosclerosis 1986; 60: 141–9PubMedCrossRef

75.

Cristofori M, Mastacchi R, Barbanti M, et al. Pharmacokinetics and distribution of a fluoresceinated glycosaminoglycan, sulodexide, in rats: part I. Pharmacokinetics in rats. Arzneimittel-Forschung / Drug Research 1985; 35(2): 1513–6

76.

Ruggeri A, Guizzardi S, Franchi M, et al. Pharmacokinetics and distribution of a fluoresceinated glycosaminoglycan, sulodexide, in rats: part II. Organ distribution in rats. Arzneimittel-Forschung / Drug Research 1985; 35(2): 1517–9

77.

Keryx Biopharmaceuticals, Inc. Data on file, 2007

78.

Mauro M, Ferraro G, Palmieri GC, et al. Profibrinolytic and antithrombotic effects of sulodexide; a double-blind, crossover, placebo-controlled study. Curr Ther Res 1992; 51: 342–50

79.

Busutti L, Breccia A. Pharmacokinetics of sulodexide after single oral administration in man. Euro J Clin Res 1991; 1: 25–36

80.

Milani MR, Busutti L, Breccia A, et al. Pharmacokinetics of sulodexide evaluated from ¹³¹I-labelled fast moving heparin after single intravenous and oral administration of different does in man. Br J Clin Res 1992; 3: 161–78

81.

Breccia A, Busutti L, Fini A. Pharmacokinetics of sulodexide evaluated from labelled fast moving heparin and from labelled dermatan sulfate after single intravenous and oral administration. Euro J Clin Res 1992; 3: 97–113

82.

Solini A, Vergnani L, Ricci F, et al. Glycosaminoglycans delay the progression of nephropathy in NIDDM. Diabetes Care 1997; 20(5): 819–23PubMedCrossRef

83.

Velussi M, Cernigoi AM, Dapas F, et al. Glycosaminoglycans oral therapy reduces microalbuminuria, blood fibrinogen levels and limb arteriopathy clinical signs in patients with non-insulin dependent diabetes mellitus. Diabetes Nutr Metab 1996; 9: 53–8

84.

Poplawska A, Szelachowska M, Topolska J, et al. Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria. Diabetes Res Clin Pract 1997; 38: 109–14PubMedCrossRef

85.

Solini A, Vergnani L, Ricci F, et al. Therapy with glycosaming-lycans lowers excretion rate in non-insulin dependent diabetic patients with microalbuminuria. Diab Nutr Metab 1991; 7: 304–7

86.

Dedov I, Shestakova M, Vorontzov A, et al. A randomized controlled study of sulodexide therapy for the treatment of diabetic nephropathy. Nephrol Dial Transplant 1997; 12: 2295–300PubMedCrossRef

87.

Szelanowska M, Poplawska A, Topolska J, et al. A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type 1 diabetic patients. Curr Med Res Opin 1997; 13: 539–45PubMedCrossRef

88.

Skrha J, Perusicova J, Pontuch P, et al. Glycosaminoglycan sulodexide decreases albuminuria in diabetic patients. Diabetes Res Clin Pract 1997; 38: 25–31PubMedCrossRef

89.

Sorrenti G, Grimaldi M, Canova N, et al. Glycosaminoglycans as a possible tool for micro- and macroalbuminuria in diabetic patients: a pilot study. J Int Med Res 1997; 25: 81–6PubMed

90.

Oksa A, Pontuch P, Kratochvilova H, et al. The effects of glycosaminoglycan sulodexide on albuminuria in patients with diabetes mellitus. Bratisl Lek Listy 1999; 100: 486–9PubMed

91.

Gambaro G, Kimacska 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: 1615–25CrossRef

92.

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): 568–74PubMed

93.

Lewis EJ, Lewis JB, Hunsicker LG. Interim analysis of a pilot trial of sulodexide type 2 diabetic nephropathy with microalbuminuria [abstract]. J Am Soc Nephrol 2005; 16: 58ACrossRef

94.

Condorelli M, Chiariello M, Dagianti A, et al. IPO-V2: a prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction. J Am Coll Cardiol 1994; 23: 27–34PubMedCrossRef

95.

Coccheri S, Scondotto G, Agnelli G, et al. Sulodexide in the treatment of intermittent claudication: results of a randomized, double-blind, multicentre, placebo-controlled study. Euro Heart J 2002; 23: 1057–65CrossRef

96.

96. Lambers-Heerspink HJ, Fowler MJ, Volgi J. Rationale for and study design of the sulodexide trials in type 2 diabetic hypertensive patients with microalbuminuria or over nephropathy. Diabet Med. In press

Titel: The Role of Sulodexide in the Treatment of Diabetic Nephropathy
verfasst von: Dr Ram Weiss
Robert Niecestro
Itamar Raz
Publikationsdatum: 01.12.2007
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 18/2007
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200767180-00004

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 18/2007

Darunavir in the Treatment of HIV-1 Infection

Acknowledgement

Histamine and Leukotriene Receptor Antagonism in the Treatment of Allergic Rhinitis

Treatment of Lysosomal Storage Disorders

Induction Therapy in Renal Transplantation

Rosiglitazone