NDT Advance Access originally published online on December 18, 2007
Nephrology Dialysis Transplantation 2008 23(6):1946-1954; doi:10.1093/ndt/gfm893
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Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria
1 Department of Clinical Pharmacology, University Medical Center, Groningen, The Netherlands 2 Division of Clinical Epidemiology, University of Utah, Salt Lake City, UT 3 Vanderbilt University College of Medicine, Nashville, TN, USA 4 Hadassah University Medical Center, Jerusalem, Israel 5 The Collaborative Study Group, Chicago, IL 6 University of Iowa College of Medicine, Iowa City, IA 7 Diabetes and Glandular Disease, Research Associates, San Antonio, TX 8 Research Institute of Dallas, Dallas, TX 9 Southern Arizona VA Health Care System, Tucson, AZ 10 Georgetown University Medical Center, Washington, DC 11 Model Clinical Research, North Baltimore, MD 12 University of Kansas City Medical Center and College of Health Sciences, Veterans Affairs Medical Center, Kansas City, MO, USA
Correspondence and offprint requests to: H. J. Lambers Heerspink, Department of Clinical Pharmacology University Medical Center Groningen, University of Groningen, A. Deusinglaan, 19713 AV Groningen, The Netherlands. Tel: +31-50-363-2809; Fax: +31-50-363-2812; E-mail: H.J.Lambers.Heerspink{at}med.umcg.nl
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Abstract |
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Background. Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months’ therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial.
Methods. A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization.
Results. The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed.
Conclusion. Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.
Keywords: diabetes; microalbuminuria; randomized clinical trial; sulodexide
Received for publication: 6. 9.07
Accepted in revised form: 23.11.07