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Promising kidney drug fails in large clinical trial
Oct 28, 11 Clinical UpdatesWhat was hoped to be a promising new drug to protect the kidneys has failed to benefit diabetes patients with kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The results call into question the usefulness of the drug sulodexide.
Kidney disease due to diabetes is the most common cause of kidney failure in developed countries. The number of patients with type 2 diabetes is expected to double and reach 366 million individuals worldwide by 2030. Kidney disease cases are sure to rise in parallel.
Investigators have wondered whether sulodexide, which belongs to a class of drugs called glycosaminoglycans, may protect the kidneys. The drug is actually a naturally occurring compound and has been used for more than 20 years to treat various heart conditions. Previous research indicates that sulodexide reduces excretion of protein in the urine, which is a hallmark of kidney disease.
To test the effects of sulodexide on the kidneys in a large and extensive trial, David Packham, MD (Melbourne Renal Research Group, in Australia) and his colleagues within the Collaborative Study Group (a large clinical trial group comprised of various kidney care centers) conducted a randomized, double-blind, placebo-controlled study in patients with diabetes and kidney disease. The investigators planned to enroll 2,240 patients in the Sun-MACRO trial over a period of two years, but they stopped the study early after enrolling 1,248 patients because they did not detect any significant differences between sulodexide and placebo for preventing kidney failure. Also, the trial did not confirm the potentially beneficial effect of sulodexide in reducing urinary protein excretion that was previously reported in smaller studies.
Sulodexide is a highly purified mixture of glycosaminoglycans composed of low molecular weight heparin (80%) and dermatan sulfate (20%).
Use of sulodexide in patients with peripheral vascular disease
Sulodexide is a highly purified glycosaminoglycan containing a combination of heparan sulfate with affinity for antithrombin III and dermatan sulfate with affinity for heparin cofactor II. This antithrombotic and antithrombin activity is of great pharmacologic interest and makes sulodexide a suitable drug for the prophylaxis and treatment of arterial and venous peripheral diseases. In arterial pathology, changes in the Winsor Index, improvement in peripheral blood flow, and reduction in pain-free walking distance confirm that treatment with oral sulodexide is effective. Lipid components linked to the genesis of peripheral vascular processes, including triglycerides, total cholesterol, and low-density lipoprotein fractions, as well as plasma and blood viscosity, are reduced by the administration of sulodexide, whereas the high-density lipoprotein fraction increases. Sulodexide inhibits aggregation and adhesion of platelets at the level of the vascular wall, reduces plasma fibrinogen concentrations, reduces plasminogen activator inhibitor-1, and increases tissue plasminogen activator, as well as systemic fibrinolytic and thrombolytic activity, thereby demonstrating efficacy in the treatment of thromboembolic disease. There is no interaction between sulodexide and other drugs used as long-term treatment for peripheral vascular disease.“In view of the negative results of Sun-MICRO trial and the data analysis from this study, it is tempting to conclude that sulodexide has no therapeutic benefit in type 2 diabetic nephropathy,” the authors wrote.
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Study co-authors include Rory Wolfe, PhD, Anne Reutens, MD, Sara Ivory, Robert Atkins, MD (Monash University, in Melbourne, Australia); Tomas Berl, MD (University of Colorado, in Denver); Hiddo Lambers Heerspink, PhD, Dick de Zeeuw, MD, PhD (University Medical Centre Groningen, in the Netherlands); Richard Rohde (the Collaborative Study Group); Julia Lewis, MD (Vanderbilt University Medical Center); Itamar Raz, MD (Hadaza Hebrew University, in Jerusalem, Israel); Thomas Wiegmann, MD (Veterans Affairs Medical Center, in Kansas City); Juliana Chan, MD (Prince of Wales Hospital, in Hong Kong, China); and Edmund Lewis, MD (Rush University Medical Center); for the Collaborative Study Group.
Disclosures: This study was funded entirely by Keryx Biopharmaceuticals.
The article, entitled “Sulodexide Fails to Demonstrate Renoprotection in Overt Type 2 Diabetic Nephropathy,” will appear online at http://jasn.asnjournals.org/ on Thursday, October 27, 2011, doi:10.1681/ASN.2011040378.
The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.
Founded in 1966, and with more than 12,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.
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Sulodexide does not prevent kidney failure in diabetes patients with kidney disease
* Suloxdexide is no better than placebo at preventing kidney failure or reducing urinary protein excretion in diabetes patients with kidney failure.
* Kidney disease due to diabetes is the most common cause of kidney failure in developed countries.
* The prevalence of type 2 diabetes is expected to double by 2030. Kidney disease cases are sure to rise in parallel.###
Shari Leventhal
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202-640-1394
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