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Romanian Journal of Internal Medicine

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Efficacy of long-term low-dose sulodexide in diabetic and non-diabetic nephropathies

Diana-Silvia Zilişteanu
  • Corresponding author
  • Center of Internal Medicine and Nephrology, Fundeni Clinical Institute, Bucharest
  • “Carol Davila” University of Medicine and Pharmacy, Bucharest
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Teodora Atasie / M. Voiculescu
  • Center of Internal Medicine and Nephrology, Fundeni Clinical Institute, Bucharest
  • “Carol Davila” University of Medicine and Pharmacy, Bucharest
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-10-14 | DOI: https://doi.org/10.1515/rjim-2015-0022


Background and Aims. Sulodexide has been reported to have antiproteinuric and nephroprotective properties. We investigated the effects of long-term low-dose Sulodexide on proteinuria and renal function in patients with chronic kidney disease (CKD) caused by diabetic nephropathy (DN), hypertensive nephropathy (HN) and primary glomerulonephritis (GN).

Material and Methods. 100 patients with CKD received low-dose Sulodexide 50 mg/day for 12 months. Treatment efficacy was evaluated as proteinuria reduction compared to baseline; response was defined as a decline in proteinuria below 0.3 g/d. Renal function evolution was assessed by eGFR variation from baseline.

Results. All patients presented reduction of proteinuria, with global mean value of proteinuria decrease of 0.85 ± 1.34 g/d (p<0.0001). Patients with HN had the highest mean percentage of proteinuria reduction (73±29%) and the lowest mean time period to achieve responder status (6.6±2.4 months), compared to patients with DN (57±29%, 8±2.9 months) and GN (63±24%, 10.7±1.2 months). Renal function as mean eGFR remained stable or improved during the study; significant increase was found only in HN group (3.41 ± 6.38 ml/min/1.73m2, p=0.043). Multivariate regression analysis identified that responder status was significantly associated with gender, baseline eGFR, baseline proteinuria and etiology of CKD. Concomitant administration of ACEIs or/and ARBs did not influence the response to Sulodexide therapy.

Conclusions. Independently of ACEIs or/and ARBs therapy, long-term low-dose Sulodexide is efficient as antiproteinuric and renoprotective therapy in patients with CKD caused by DN, GN and HN. Better response is achieved in patients with lower degree of renal dysfunction.

Obiectivul studiului. Sulodexid a demonstrat că posedă proprietăţi antiproteinurice şi nefroprotectoare, motiv pentru care am decis să investigăm efectele unei doze mici de Sulodexid administrate pe termen lung asupra proteinuriei şi funcţiei renale la pacienţi cu boală cronică de rinchi (BCR) apărută ca urmare a nefropatiei diabetice (ND), hipertensive (NH) sau glomerulonefritelor primare (GN).

Material şi Metodă. 100 de pacienţi cu BCR au primit în fiecare zi câte o doză mică de Sulodexid (50 mg/zi) timp de 12 luni. Eficacitatea tratamentului a fost evaluată prin reducerea nivelurilor proteinuriei comparativ cu valorile iniţiale; răspunsul terapeutic a fost definit drept o scădere a proteinuriei la valori mai mici de 0.3 g/dl. Evoluţia funcţiei renale a fost evaluată prin calcularea variaţiei eGFR faţă de valoarea iniţială.

Rezultate. La finalul celor 12 luni de tratament cu Sulodexid, toţi pacienţii au înregistrat o scădere semnificativă a proteinuriei, cu o valoare globală medie a scăderii proteinuriei de 0.85 ± 1.34 g/dl (p<0.0001). Pacienţii cu NH au înregistrat cea mai ridicată valoare medie procentuală a scăderii proteinuriei (73±29%) şi cea mai redusă durată medie a tratamentului până la obţinerea răspunsului terapeutic (6.6±2.4 luni), comparativ cu pacienţii cu ND (57±29%, 8±2.9 luni) şi GN (63±24%, 10.7±1.2 luni). Funcţia renală ca şi medie eGFR a rămas nemodificată sau s-a ameliorat, o ameliorare semnificativă fiind înregistrată doar în grupul pacienţilor cu NH (3.41 ± 6.38 ml/min/1.73m2, p=0.043). Analiza regresiei multivariate a identificat că răspunsul terapeutic a fost semnificativ asociat cu sexul, valorile iniţiale ale GFR, proteinuriei şi cu etiologia BCR. Administrarea concomitentă de inhibitori ai enzimei de conversie (IEC) sau/şi blocanţi ai receptorilor angiotensinei (BRA) nu au influenţat răspunsul terapeutic al administrării de Sulodexid.

Concluzii. Sulodexid în doză mică pe termen lung a dovedit eficienţă terapeutică în ceea ce priveşte efectul său antiproteinuric şi renoprotectiv la pacienţii cu BCR cauzată de ND, NH sau GN, independent de administrarea de IEC/BRA. Un răspuns terapeutic mai bun a fost înregistrat la pacienţii aflaţi în stadii mai puţin avansate ale disfuncţiei renale.

Keywords: sulodexide; nephropathy; proteinuria; renal function; CKD progression


  • 1. MASOLA V, ZAZA G, GAMBARO G. Sulodexide and glycosaminoglycans in the progression of renal disease. Nephrol Dial Transplant 2014; 29: i74-i79.Web of ScienceGoogle Scholar

  • 2. LAUVER DA, LUCCHESI BR. Sulodexide: a renewed interest in this glycosaminoglycan. Cardiovascular Drug Reviews 2006; 24(3-4): 214-226.CrossrefGoogle Scholar

  • 3. LAUVER DA, LUCCHESI BR. Sulodexide: A renewed interest in this glycosaminoglycan. Cardiovascular Drug Reviews 2006; 24(3–4): 214–226. 2CrossrefGoogle Scholar

  • 4. MANELLO F, MEDDA V, LIGI D, RAFFETTO JD. Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: possible pharmacological role against collagen degradation in vascular chronic diseases. Curr Vasc Pharm 2013; 11: 354-365.Web of ScienceGoogle Scholar

  • 5. BROEKHUIZEN LN, LEMKES BA, MOOIJ HL et al. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia 2010; 53: 2646–2655.Web of ScienceGoogle Scholar

  • 6. KRISTOVA V, LISKOVA S, SOTNIKOVA R et al. Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats. Physiol Res 2008; 57: 491–494.Google Scholar

  • 7. COFFEY AK, KARNOVSKY MJ. Heparin inhibits mesangial cell proliferation in habu-venom-induced glomerular injury. Am J Pathol 1985; 120: 248–255.Google Scholar

  • 8. LEWIS EJ, XU X. Abnormal glomerular permeability characteristics in diabetic nephropathy: implications for the therapeutic use of low-molecular weight heparin. Diabetes Care 2008; 31(Suppl 2): S202–S207.CrossrefWeb of ScienceGoogle Scholar

  • 9. CEOL M, GAMBARO G, SAUER U et al. Glycosaminoglycan therapy prevents TGF-beta1 overexpression and pathologic changes in renal tissue of long term diabetic rats. J Am Soc Nephrol 2000; 11: 2324–2336.Google Scholar

  • 10. MASOLA V, ONISTO M, ZAZA G, LUPO A, GAMBARO G. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J Translational Medicine 2012; 10: 213.CrossrefWeb of ScienceGoogle Scholar

  • 11. GADDI A, CICERO AFG, GAMBARO G. Nephroprotective action of glycosaminoglycans: why the pharmacological properties of Sulodexide might be reconsidered. Int J Nephrol Renovasc Dis 2010; 3: 99-105.Google Scholar

  • 12. SOLINI A, CARRARO A, BARZON I et al. Therapy with glycosaminoglycans lowers albumin excretion rate in non-insulin dependent diabetic patients with microalbuminuria. Diab Nutr Metab 1994; 7: 304–307.Google Scholar

  • 13. 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: 1615–1625.CrossrefGoogle Scholar

  • 14. BLOUZA S, DAKHLI S, ABID H et al. Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy. J Nephrol 2010; 23: 415–424.Google Scholar

  • 15. ROZITA M, MD SHAHRIR MS, LOO CY et al. Glycosaminoglycans (sulodexide) for resistant heavy proteinuria of chronic glomerulonephritides. Nephrology 2008; 13(Suppl 1): A13.Google Scholar

  • 16. BANG K, CHIN HJ, CHAE DW et al. Anti-proteinuric effect of sulodexide in Immunoglobulin A Nephropathy. Yonsei Med J 2011; 52: 588–594.CrossrefWeb of ScienceGoogle Scholar

  • 17. PALATINI P. Glomerular hyperfiltration: a marker of early renal damage in pre-diabetes and pre-hypertension. Nephrol Dial Transplant 2012; 27: 1708-1714.Web of ScienceGoogle Scholar

  • 18. CHRISTIANSEN REF, TENSTAD O, LEH S, IVERSEN BM. Glomerular charge selectivity is impaired in hypertensive nephropathy. Nephrol Dial Transplant, 2004; 19: 1083-1091.Google Scholar

  • 19. HEERSPINK HL, GREENE T, LEWIS JB, et al. Collaborative Study Group. Effects of Sulodexide in patients with type 2 diabetes and persistent albuminuria. Nephrol Dial Transplant 2008; 23(6):1946–1954.Web of ScienceGoogle Scholar

  • 20. LI P, MA LL, XIE RJ, et al. Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure. Acta Pharmacologica Sinica 2012; 33: 644–651.CrossrefWeb of ScienceGoogle Scholar

About the article

Published Online: 2015-10-14

Published in Print: 2015-06-01

Citation Information: Romanian Journal Of Internal Medicine, Volume 53, Issue 2, Pages 161–169, ISSN (Online) 1220-4749, DOI: https://doi.org/10.1515/rjim-2015-0022.

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© 2015 Diana-Silvia Zilişteanu et al., published by De Gruyter Open. This chapter is distributed under the terms of the Creative Commons Attribution 4.0 Public License. BY 4.0

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