Effects of glycosaminoglycans on the glomerular changes induced by Adriamycin

Glycosaminoglycans can stimulate the synthesis of glomerular basement membrane (GBM) proteins by glomerular cells and correct biochemical alterations of the GBM. In this study we examine the effects of heparin and low-molecular-weight heparin (LMWH) on glomerular permeability to proteins and glomerular structure in Adriamycin-treated rats. One Adriamycin dose of 5 mg/kg body weight was administered i.v. to 38 female Wistar rats. Eleven animals were also treated with heparin (250 U) administered s.c. twice daily and 7 with LMWH 6 mg/kg body weight administered s.c. twice daily. Urine samples were collected before and 30 and 60 days after the beginning of treatment to quantify albumin excretion and to characterize urinary proteins by gel filtration and electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Blood samples were also collected on day 60 from these rats to estimate renal permeability by gel filtration; the rats were then killed and the kidneys removed for histological analysis. Heparin administration caused a reduction in urinary albumin excretion and in the incidence of segmental glomerulosclerosis in Adriamycin-treated rats. However, heparin did not modify the selectivity of the GBM to proteins of different molecular weights. These data suggest that the effect of heparin on albuminuria may be due to changes in the negative GBM charges induced by this drug.