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

Decreased expression of heparan sulphate has been shown in theglomerular basement membrane of patients with overt diabeticnephropathy. Low-molecular-weight heparin (LMWH) is a highlysulphated glycosaminoglycan with strong structural and functionalsimilarities to heparan sulphate. In a first study, we set outto assess if LMWH could decrease the urinary albumin excretionrate (AER) in diabetic patients with overt nephropathy. Sixpatients entered a randomized, double-blind, placebo-controlledcrossover study with treatment episodes of 1 month, separatedby a 1-month wash-out. Patients self-administered prefilledsyringes with either placebo or LMWH (enoxaparin 40 mg/0.4 ml)at bedtime. Baseline AER levels before either treatment periodwere similar. In contrast to placebo, AER significantly decreasedfrom 447 (181—1102) to 295 (100—873) µg/minafter 1 month treatment with LMWH (P<0.05). Compared to placebo,the effect of LMWH did not reach statistical significance inthese six patients after 1 month treatment (P=0.16). Haemodynamicvariables including glomerular filtration rate and filtrationfraction did not change during enoxaparin treatment. We observed a favourable effect on AER during LMWH treatmentin diabetic patients with overt nephropathy. These data suggestthat long-term treatment trials in a larger group of patientsmay potentially demonstrate a new therapeutic option for patientswith overt diabetic nephropathy.