chondroitin-sulfates and Proteinuria

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.

Topics: Adult; Aged; Analysis of Variance; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Retinopathy; Double-Blind Method; Drug Combinations; Endothelium, Vascular; Exudates and Transudates; Female; Follow-Up Studies; Heparitin Sulfate; Humans; Kidney Function Tests; Male; Middle Aged; Proteinuria; Reference Values; Statistics, Nonparametric; von Willebrand Factor

Diabetic nephropathy is a progressive renal disease with thickening of the glomerular basement membrane and mesangial expansion and proliferation as histological hallmarks. The presence of the glycosaminoglycan side chains of heparan sulfate proteoglycan, an important constituent of the glomerular basement membrane, is decreased in diabetic nephropathy proportionally to the degree of proteinuria. Danaparoid sodium is a mixture of sulfated glycosaminoglycans consisting mainly of heparan sulfate. The study presented here involved performing a randomized placebo-controlled crossover study with danaparoid sodium in diabetic patients with overt proteinuria. The aim of the study was to evaluate the effect on proteinuria and safety/tolerability. Nine patients completed the study, without major side effects; the crossover study consisted of two 6-wk periods of treatment with 750 anti-Xa units danaparoid sodium subcutaneously once-daily or placebo. Following danaparoid sodium, significant declines of both albuminuria and proteinuria were found. After danaparoid sodium, the albumin excretion ratio standardized for urinary creatinine reduced with 17% in comparison with an increase of 23% after placebo (95% confidence interval of the difference,-75.9-3.9%; P = 0.03). The percentage change of the urinary protein excretion corrected for urinary creatinine differed at 8 wk significantly between both treatment arms (P = 0.001). Additional parameters for safety as hematological, hemostasis, biochemical parameters, and fundusphotography did not show any clinically significant difference for both groups. Only two patients had minor skin hematomas at the injection site while using danaparoid sodium. In conclusion, the supplementation was found to be feasible and was not associated with side effects. A significant decline of proteinuria was found. More prospective dose-finding and long-term studies must be performed to see whether danaparoid sodium could not only induce a reduction of proteinuria but also halt the progression of renal disease.

Topics: Adult; Chondroitin Sulfates; Cross-Over Studies; Dermatan Sulfate; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Double-Blind Method; Drug Combinations; Female; Heparinoids; Heparitin Sulfate; Humans; Male; Middle Aged; Proteinuria; Treatment Outcome

Topics: Child; Chondroitin Sulfates; Diabetes Mellitus; Glomerulonephritis; Glycosaminoglycans; Heparitin Sulfate; Humans; Mucopolysaccharidoses; Nephritis, Hereditary; Nephrotic Syndrome; Proteinuria

The authors have studied the hyperlipaemia, which occurs 24 hours after immunisation. This hyperlipaemia is related to the stress induce by the immunisation process, associated with an increase of serum of glycoproteins. this glycoproteins inhibit the clearing factor and prevent the hydrolysis of triglycerides, which acumulate in blood. A similar increase of glycosaminoglycans is observed in urine (type IV chondroitine sulfate).

Topics: Amino Sugars; Animals; Carbohydrates; Chondroitin Sulfates; Erythrocytes; Glycoproteins; Glycosaminoglycans; Immunization; Lipids; Proteinuria; Rabbits; Sialic Acids; Time Factors; Uronic Acids