Skip to main content
SpringerLink
Log in

The Role of Glycosaminoglycans and Sulodexide in the Treatment of Diabetic Nephropathy

  • Leading Article
  • Published:
Treatments in Endocrinology

Abstract

Diabetic nephropathy occurs in 20–40% of diabetic patients, making it one of the most important causes of end-stage renal disease (ESRD). It has a large impact in terms of associated morbidity and mortality for the individual patient and in terms of costs for healthcare. Several studies have demonstrated that micro- and macroalbuminuria predict cardiovascular morbidity and mortality in patients with diabetes mellitus.

Current nephroprotective therapies for diabetic nephropathy include the pursuit of normoglycemia and normotension, and a consensus is emerging that there is a necessity to also achieve as low a level of albuminuria as possible. However, the search for innovative and ancillary approaches to the prevention and treatment of this diabetic complication is warranted since strict metabolic control can be difficult, and sometimes dangerous, to achieve and even diabetic patients responding to ACE inhibitors (ACEIs) or angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and metabolic control show progressive renal damage and eventually ESRD. A number of drugs are currently being investigated; glycosaminoglycans are particularly interesting since, in theory, they target the generalized endothelial dysfunction and metabolic defect in matrix and basement membrane synthesis which, according to the Steno hypothesis, are responsible for diabetic nephropathy and macroangiopathy.

Treatment with glycosaminoglycans, and with sulodexide in particular, significantly improves albuminuria in type 1 and type 2 diabetic patients with micro- or macroalbuminuria. The albuminuria-lowering effect of sulodexide enhances the effect of ACEI/ARB therapy. Most studies have shown that the effect of sulodexide on albuminuria is sustained, strongly suggesting that favorable chemical and anatomic remodeling is induced by exogenous glycosaminoglycans in renal tisues, as observed in the experimental model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III

Similar content being viewed by others

Notes

  1. When it refers to therapeutics, the term GAGs is generally used in the text to indicate a broad category of molecules including heparin(s), low-molecular weight heparin(s), heparan sulfate, dermatan sulfate, and mixed formulations of GAGs, such as sulodexide and danaparoid sodium, because they share the same biologic and ‘nephroprotective’ effects. Specific GAG molecules have been defined, where necessary.

References

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

    Article  PubMed  CAS  Google Scholar 

  2. 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: 2156–64

    Article  PubMed  CAS  Google Scholar 

  3. Gilbert RE, Cooper ME, McNally PG, et al. Microalbuminuria: prognostic and therapeutic implications of diabetes mellitus. Diabet Med 1994; 11: 636–45

    Article  PubMed  CAS  Google Scholar 

  4. Borch-Johnsen K, Kreiner S. Proteinuria value as a predictor of cardiovascular mortality in insulin dependent diabetes mellitus. BMJ 1987; 294: 1651–4

    Article  PubMed  CAS  Google Scholar 

  5. Rossing P, Hougaard P, Borch-Johnsen K, et al. Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study. BMJ 1996; 313: 779–84

    Article  PubMed  CAS  Google Scholar 

  6. Deckert T. Glycemic control and complications. In: Alberti KGMM, Krall LP, editors. The diabetes annual 4. Amsterdam: Elsevier Science Publishers BV, 1988: 496–518

    Google Scholar 

  7. Osterby R. Glomerular structural changes in type I diabetes mellitus: causes, consequences, and prevention. Diabetologia 1992; 35: 803–12

    Article  PubMed  CAS  Google Scholar 

  8. Kofoed-Enedvoldsen A. Heparan sulphate in the pathogenesis of diabetic nephropathy. Diabetes Metab Rev 1995; 11: 137–60

    Article  Google Scholar 

  9. Gambaro G, Ceol M, Antonello A. The Steno hypothesis for cardiovascular and renal disease revisited. In: Mogensen CE, editor. The kidney and hypertension in diabetes mellitus. 6th ed. Boston (MA): Kluwer Academic Publishers, 2003: 27–43

    Google Scholar 

  10. Remuzzi G, Bertani T. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? Kidney Int 1990; 38: 384–94

    Article  PubMed  CAS  Google Scholar 

  11. Eddy AA, McCulloch L, Liu E, et al. A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. Am J Pathol 1991; 138: 1111–23

    PubMed  CAS  Google Scholar 

  12. Keane WF, Brenner BM, de Zeeuw D, et al. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int 2003; 63: 1499–507

    Article  PubMed  Google Scholar 

  13. Atkins RC, Briganti EM, Lewis JB, et al. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis 2005; 45: 281–7

    Article  PubMed  Google Scholar 

  14. De Zeeuw D. Albuminuria, not only a cardiovascular/renal risk marker, but also a target for treatment. Kidney Int 2004; 66Suppl. 91: S2–6

    Article  Google Scholar 

  15. DCCT 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: 977–86

    Article  Google Scholar 

  16. Parving HH, Hovind P, Rossing K, et al. Evolving strategies for renoprotection: diabetic nephropathy. Curr Opin Nephrol Hypertens 2001; 10: 515–22

    Article  PubMed  CAS  Google Scholar 

  17. Gansevoort RT, Sluiter WJ, Hemmelder MH, et al. Antiproteinuric effect of bloodpressure-lowering agents: a meta-analysis of comparative trials. Nephrol Dial Transplant 1995; 10: 1963–74

    PubMed  CAS  Google Scholar 

  18. Gansevoort RT, de Zeeuw D, de Jong PE. Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? Kidney Int 1994; 45: 861–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–8

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. 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; 345: 861–9

    Article  PubMed  CAS  Google Scholar 

  23. Parving HH, Rossing P. The use of antihypertensive agents in prevention and treatment of diabetic nephropathy. Curr Opin Nephrol Hypertens 1994; 3: 292–300

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348: 383–93

    Article  PubMed  Google Scholar 

  28. Gambaro G, Skrha J, Ceriello A. Glycosaminoglycan therapy for long-term diabetic complications? Diabetologia 1998; 41: 975–9

    Article  PubMed  CAS  Google Scholar 

  29. Tamsma JT, van den Born J, Brujin JA, et al. Expression of glomerular extracellular matrix components in human diabetic nephropathy: decrease of heparan sulphate in the glomerular basement membrane. Diabetologia 1994; 37: 313–20

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  32. Oshima Y, Isogai S, Mogami K, et al. Protective effect of heparin on renal glomerular anionic sites of streptozotocin-injected rats. Diabetes Res Clin Pract 1995; 25: 83–9

    Article  Google Scholar 

  33. Oturai PS, Rasch R, Hasseleger E, et al. Effects of heparin and aminoguanidine on glomerular basement membrane thickening in diabetic rats. APMIS 1996; 104: 259–64

    Article  PubMed  CAS  Google Scholar 

  34. Oturai PS. Effects of heparin on vascular dysfunction in diabetic rats. Clin Exp Pharmacol Physiol 1999; 26: 411–4

    Article  PubMed  CAS  Google Scholar 

  35. Van der Pijl JW, Lemkes HH, Frolich M, et al. Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2. J Am Soc Nephrol 1999; 10: 1331–6

    PubMed  Google Scholar 

  36. Nielsen S, Schmitz A, Bacher, et al. Transcapillary escape rate and albuminuria in type II diabetes: effects of short-term treatment with low-molecular weight heparin. Diabetologia 1999; 42: 60–7

    Article  PubMed  CAS  Google Scholar 

  37. Striker GE, Lupia E, Elliot S, et al. Glomerulosclerosis, arteriosclerosis, and vascular graft stenosis: treatment with oral heparinoids. Kidney Int Suppl 1997; 63: S120–3

    PubMed  CAS  Google Scholar 

  38. Engelberg H. Actions of heparin in the atherosclerotic process. Pharmacol Rev 1996; 48: 327–52

    PubMed  CAS  Google Scholar 

  39. Park HY, Kang S, Kim GY, et al. Inhibition of neointimal proliferation of rat carotid artery by sulodexide. J Korean Med Sci 1997; 12: 210–4

    PubMed  CAS  Google Scholar 

  40. Gambaro G, Baggio B. Glycosaminoglycans: a new paradigm in the prevention of proteinuria and progression of glomerular disease. Nephrol Dial Transplant 1996; 11: 762–4

    Article  PubMed  CAS  Google Scholar 

  41. Ceol M, Gambaro G, Nerlich A, et al. Glycosaminoglycan therapy prevents TGF-β1 over-expression and pathological changes in renal tissue of long-term diabetic rats. J Am Soc Nephrol 2000; 11: 2324–36

    PubMed  CAS  Google Scholar 

  42. Bobadilla NA, Tack I, Tapia E, et al. Pentosan polysulfate prevents glomerular hypertension and structural injury despite persisting hypertension in 5/6 nephrectomy rats. J Am Soc Nephrol 2001; 12: 2080–7

    PubMed  CAS  Google Scholar 

  43. Koppel H, Yard BA, Christ M, et al. Modulation of angiotensin II-mediated signalling by heparan sulphate glycosaminoglycans. Nephrol Dial Transplant 2003; 18: 2240–7

    Article  PubMed  Google Scholar 

  44. Xu X, Rao G, Maxhimer 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: 673A

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  46. 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: 175–84

    PubMed  CAS  Google Scholar 

  47. Ceol M, Nerlich A, Baggio B, et al. Increased glomerular β1(IV) collagen expression and deposition in long-term diabetic rats is prevented by chronic glycosaminoglycan treatment. Lab Invest 1996; 74: 484–95

    PubMed  CAS  Google Scholar 

  48. Weigert C, Brodbeck K, Haring HU, et al. Low-molecular-weight heparin prevents high glucose- and phorbol ester-induced TGF-β1 gene activation. Kidney Int 2001; 60: 935–43

    Article  PubMed  CAS  Google Scholar 

  49. Webb LM, Ehrengruber MU, Clark-Lewis I, et al. Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. Proc Natl Acad Sci U S A 1993; 90: 7158–62

    Article  PubMed  CAS  Google Scholar 

  50. Ceol M, Vianello D, Schleicher E, et al. Heparin reduces glomerular infiltration and TGF-β protein expression by macrophages in puromycin glomerulosclerosis. J Nephrol 2003; 16: 210–8

    PubMed  CAS  Google Scholar 

  51. 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: 1615–25

    Article  PubMed  CAS  Google Scholar 

  52. Feldt-Rasmussen B. Microalbuminuria, endothelial dysfunction and cardiovascular risk. Diabetes Metab 2000; 26Suppl. 4: 64–6

    PubMed  CAS  Google Scholar 

  53. Solini A, Carraro A, Barzon I, et al. Therapy with glycosaminoglycans lowers albumin excretion rate in non-insulin dependent diabetic patients with microalbuminuria. Diabetes Nutr Metab 1994; 7: 304–7

    Google Scholar 

  54. Myrup B, Hansen PM, Jensen T, et al. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus. Lancet 1995; 345: 421–2

    Article  PubMed  CAS  Google Scholar 

  55. Tamsma JT, van der Woude FJ, Lemkes HHPJ. Effect of sulfated glycosaminoglycans on albuminuria in patients with overt diabetic (type-1) nephropathy. Nephrol Dial Transplant 1996; 11: 182–5

    Article  PubMed  CAS  Google Scholar 

  56. Van der Pijl JW, van der Woude FJ, Geelhoed-Duijvestijn PHLM, et al. Danaparoid sodium lowers proteinuria in diabetic nephropathy. J Am Soc Nephrol 1997; 8: 456–62

    PubMed  Google Scholar 

  57. 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: 109–14

    Article  PubMed  CAS  Google Scholar 

  58. 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: 81–6

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Dedov I, Shestakova M, Vorontzov A, et al. A randomized, controlled study of sulodexide therapy for the treatment of diabetic nephropathy. Nephrol Dial Transplant1997; 12: 2295–300

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  62. 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

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  64. Oksa A, Pontuch P, Kratochvilova H. The effect of glycosaminoglycan sulodexide on albuminuria in patients with diabetes mellitus [in Slovak]. Bratisl Lek Listy 1999; 100: 486–9

    PubMed  CAS  Google Scholar 

  65. Achour A, Kacem M, Dibej K, et al. One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol 2005; 18: 568–74

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  67. Source Keryx Biopharmaceuticals, Inc. Press release, November 14,2005 [online]. Available from URL: http://www.shareholder.com/keryx/releases.cfm [Accessed 2006 Feb 20]

  68. Effect of sulodexide in early diabetic nephropathy [online]. Available from URL: http://www.clinicaltrials.gov/ct/gui/show/NCT00130208 [Accessed 2006 Feb 20]

  69. Effect of sulodexide in overt diabetic nephropathy. Available from URL: http://www.clinicaltrials.gov/ct/gui/show/NCT00130312 [Accessed 2006 Feb 20]

  70. Hostetter TH, Rennke HG, Brenner BM. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med 1982; 72: 375–80

    Article  PubMed  CAS  Google Scholar 

  71. Decken T, Feldt-Rasmussen B, Borch-Johnsen K, et al. Albuminuria reflects widespread vascular damage: the Steno hypothesis. Diabetologia 1988; 32: 219–26

    Google Scholar 

  72. Greive KA, Nikolic-Paterson DJ, Guimarães MAM, et al. Glomerular permselectivity factors are not responsible for the increase in fractional clearance of albumin in rat glomerulonephritis. Am J Pathol 2001; 159: 1159–70

    Article  PubMed  CAS  Google Scholar 

  73. Myers BD, Winetz F, Chui F, et al. Mechanisms of proteinuria in diabetic nephropathy: a study of glomerular barrier function. Kidney Int 1982; 21: 633–41

    Article  PubMed  CAS  Google Scholar 

  74. Hansen HP, Rossing P, Tarnow L, et al. Increased glomerular filtration rate after withdrawal of long-term antihypertensive treatment in diabetic nephropathy. Kidney Int 1995; 47: 1726–31

    Article  PubMed  CAS  Google Scholar 

  75. Reddi AS, Ramamurthi R, Miller M, et al. Enalapril improves albuminuria by preventing glomerular loss of heparan sulfate in diabetic rats. Biochem Med Metab Biol 1991; 45: 119–31

    Article  PubMed  CAS  Google Scholar 

  76. Condorelli M, Chiariello M, Daggianti 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: 27–34

    Article  PubMed  CAS  Google Scholar 

  77. Gaddi A, Galetti C, Illuminati B, et al. Meta-analysis of some results of clinical trials on sulodexide therapy in peripheral occlusive arterial disease. J Int Med Res 1996; 24: 389–406

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  79. Parnetti L, Mari D, Abate G, et al. VAscular Dementia Italian Sulodexide Study (VA.D.I.S.S.): clinical and biological results. Thromb Res 1997; 87: 225–33

    Article  PubMed  CAS  Google Scholar 

  80. Harenberg J. Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev 1998; 18: 1–20

    Article  PubMed  CAS  Google Scholar 

  81. Larsen AK, Lund DP, Langer R, et al. Oral heparin results in the appearance of heparin fragments in the plasma of rats. Proc Natl Acad Sci U S A 1986; 83: 2964–8

    Article  PubMed  CAS  Google Scholar 

  82. Van der Pijl JW, van der Woude FJ, Swart W, et al. Effect of danaparoid sodium on hard exudates in diabetic retinopathy. Lancet 1997; 350: 1743–5

    Article  PubMed  Google Scholar 

  83. Rubbi F, Caramazza R, Boccia S, et al. The effects of sulodexide on diabetic retinopathy. Minerva Cardioangiol 2000; 48Suppl. 1: 81–2

    Google Scholar 

  84. Warkentin TE, Levine MN, Hirsh J. Heparin-induced thrombocytopenia in patients treated with low-molecular weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330–5

    Article  PubMed  CAS  Google Scholar 

  85. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (Org 10172). Thromb Haemost 1993; 70: 554–61

    PubMed  CAS  Google Scholar 

  86. Hill GR, Hickton C, Henderson S, et al. The use of orgaran in heparin-induced thrombocytopenia associated with in vitro platelet aggregation at higher orgaran concentrations. Clin Lab Haematol 1997; 19: 155–7

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Prof. Gambaro has served as a consultant to Alfa Wassermann SpA, Bologna, Italy. Dr Abaterusso has no conflicts of interest that are relevant to the content of this review. Preparation of this review article was supported by the program Prin 2004 of the Italian Ministry of the University and of Scientific and Technological Research, funding Professor Gambaro.

Author information

Authors and Affiliations

  1. Department of Biomedical and Surgical Sciences, Division of Nephrology, University of Verona, Ospedale Maggiore, P.le Stefani 1, 37126, Verona, Italy

    Cataldo Abaterusso &  Giovanni Gambaro

Authors
  1. Cataldo Abaterusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanni Gambaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Gambaro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abaterusso, C., Gambaro, G. The Role of Glycosaminoglycans and Sulodexide in the Treatment of Diabetic Nephropathy. Mol Diag Ther 5, 211–222 (2006). https://doi.org/10.2165/00024677-200605040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00024677-200605040-00002

Keywords

Search

Navigation