Effect of suiphated glycosaminoglycans on albuminuria in patients with overt diabetic (type 1) nephropathy

Abstract

Decreased expression of heparan sulphate has been shown in the glomerular basement membrane of patients with over diabetic nephropathy. Low- molecular-weight heparin (LMWH) is a highly sulphated glycosaminoglycan with strong structural and functional similarities to heparan sulphate. In a first study, we set out to assess if LMWH could decrease the urinary albumin excretion rate (AER) in diabetic patients with over nephropathy. Six patients entered a randomized, double-blind, placebo-controlled crossover study with treatment episodes of 1 month, separated by a 1-month wash-out. Patients self-administered prefilled syringes with either placebo or LMWH (enoxaparin 40 mg/0.4 ml) at bedtime. Baseline AER levels before either treatment period were similar. In contrast to placebo, AER significantly decreased from 447 (181-1102) to 295 (100-873) micrograms/min after 1 month treatment with LMWH (P < 0.05). Compared to placebo, the effect of LMWH did not reach statistical significance in these six patients after 1 month treatment (P = 0.16). Haemodynamic variables including glomerular filtration rate and filtration fraction did not change during enoxaparin treatment. We observed a favourable effect on AER during LMWH treatment in diabetic patients with over nephropathy. These data suggest that long-term treatment trials in a larger group of patients may potentially demonstrate a new therapeutic option for patients with over diabetic nephropathy.

Increased Urine IgM and IgG2Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes

“…Our results extend the findings of an earlier study showing that three weeks of LMWH treatment had no effect on albuminuria in patients with type 2 diabetes [11]. These findings are in contrast to the effect seen in type 1 diabetic patients showing a reduced albuminuria during one-to-three month treatment with either unfractionated heparin or LMWH [9, 10]. The reason for this discrepancy in effects of heparins on urinary excretion of proteins between patients with type 1 and type 2 diabetes is unclear and cannot be explained by the present study.…”

Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus

“…In the present study, oral administration of sulodexide is expected to result in enhanced precursor abundance, which may drive the correction of the endothelial glycocalyx. As low-molecular-weight heparins may also exert beneficial effects on microalbuminuria and retinopathy in diabetes mellitus [30, 31], supplementation of other GAGs delivering comparable molar equivalents of glucosamine, galactosamine and glucuronic acid may share the beneficial properties of sulodexide for endothelial glycocalyx.…”

Endothelial cell injury by high glucose and heparanase is prevented by insulin, heparin and basic fibroblast growth factor

“…This suggests that with high glucose, heparanase may be produced within the cell. Heparanase activity is optimal between pH 5.0 and 6.5, with much less activity above pH 7.0 [46]. Glucose (30 mM) added for seven days to ECs lowers the medium pH (medium color become yellow) and may further stimulate heparanase activity.…”