glucuronyl-glucosamine-glycan-sulfate and Proteinuria

We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy.. A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value.. At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38±0.77 at baseline to 5.98±0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not.. A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients.

Topics: Adult; Anticoagulants; Double-Blind Method; Female; Glomerulonephritis, IGA; Glycosaminoglycans; Humans; Male; Middle Aged; Proteinuria

We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.

Topics: Animals; Axons; Blood Glucose; Body Weight; Cell Count; Diabetes Mellitus, Experimental; Electric Conductivity; Epidermis; Female; Gastric Mucosa; Glycosaminoglycans; Kidney Cortex; Myelin Sheath; Nerve Fibers; Pain Threshold; Peripheral Nerves; Peripheral Nervous System Diseases; Proteinuria; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sciatic Nerve; Skin; Superoxide Dismutase

Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats.. Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot.. Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group.. Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Biomarkers; Biphenyl Compounds; Blood Pressure; Blotting, Western; Body Weight; Creatinine; Disease Models, Animal; Fibrosis; Glycosaminoglycans; Immunohistochemistry; Irbesartan; Kidney; Kidney Failure, Chronic; Male; Nephrectomy; Nitric Oxide Synthase Type III; Proteinuria; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sclerosis; Tetrazoles; Time Factors; Tissue Plasminogen Activator; Triglycerides

Diabetic nephropathy (DN) is the most serious, life limited complication of both types of diabetes mellitus. Therefore the early identification and intensive treatment of DN is very important. DN involves the thickening of glomerular basement membrane (GBM) and the depletion of glycosaminoglycan (GAG) in the GBM with resultant diminution in the physiological electrostatic charge barrier. Additional mechanism in pathophysiology of DN is mesangial expansion. Sulodexide is glycosaminoglycan mixture of heparansulfate and dermatan sulfate. We present a 71-year old patient with severe nephrotic syndrome, probably caused by DN. AS patient refused renal biopsy, exact diagnosis of DN could not be confirmed. Since 2000 our patient was treated with sulodexide. More pronounced decrease of proteinuria was proved 1.5 year after the begin of this treatment (from 10.37 g/d to 4.8 g/d) and after 3 years was proteinuria negative.

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycosaminoglycans; Humans; Nephrotic Syndrome; Proteinuria