RENAL EFFECTS OF SHORT TERM LOW MOLECULAR WEIGHT HEPARIN ADMINISTRATION IN DIABETIC RAT MODEL

Abnormal glycosaminoglycan metabolism is involved in the pathogenesis of diabetic nephropathy. Glomerular membrane anionic charge depletion leading to albuminuria is associated with loss of glycosaminoglycan in urine. It's well known that long term administration of different types of glycosaminoglycans prevents morphological renal alterations and albuminuria in diabetic rats. This study was designed to evaluate the effect of short term administration of nadroparin calcium (a type of low molecular weight heparin) on proteinuria and to measure heparan sulphate loss in the urine in a streptosotocin diabetic rat model. Twenty, twelve weeks old wistar rats were made diabetic using streptosotocin. One group of ten rats received nadroparin calcium 200 U/kgld, whilst the second group received. 0.1 cc saline/d as control. 24 hour urine samples were collected at the begining of the study and at the end of the 6th week for determination of creatinine clearence, heparan sulphate excretion and microalbuminuria. Basal levels of microalbuminuria did not differ between nadroparin calcium and control groups (11 ± 13 mgld and 12.3 ±8 mgld respectively). At the end of the study microalbuminuria was significantly lower in the study group (2.8 ± 3.8 mgld and 28.5 ± 12 mgld respectively, p<0.05). Basal heparan sulphate excretion did not differ between two groups (104.7 ± 66.5 μ^d and 128 ± 69.5 μgld respectively). At the end of the study heparan sulphate excretion was significantly lower in the nadroparin calcium group (195 ± 96 mgld and 662 ±300 mgld respectively, p<0.01). In conclusion short term nadroparin calcium therapy may lead to reduction of microalbuminuria and heparan sulphate excretion by means of protection or replacement of the glomerular basement membrane anionic charge.