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.