Glomerular permeability to neutral and anionic dextrans in experimental diabetes

Abstract

Renal clearances of polydispersed neutral and anionic dextrans were measured in diabetic rats. In addition, urinary protein and albumin excretion rates were determined. Measurements were performed 3 months after the induction of diabetes (i.v. alloxan 50 to 55 mg/kg of body wt) in rats which were either untreated or which received supplemental insulin (6 U of NPH daily) and were compared to those in age-matched SHAM-treated rats. Fractional clearances (relative to inulin) of neutral dextrans remained unchanged in insulin-supplemented rats and were slightly but significantly increased in untreated rats. The application of an isoporous model of the glomerular filtration barrier permitted the conclusion that the size-selective characteristics of the barrier were unaltered in diabetic rats. Fractional clearances of anionic dextrans were significantly reduced 50 to 60% in both diabetic groups suggesting an increase in the negative charge density of the filtration barrier and potentially an increase in restriction to the glomerular filtration of anionic proteins. However, urinary and albumin excretions tended to increase in both groups of diabetic rats, including a 164% increase in albumin excretion in untreated rats. This apparent discrepancy between reduced dextran sulfate clearances and increased protein excretions suggests that factors other than charge-selectivity may be of major importance in determining the filtration of proteins. The marked increase in albumin excretion observed in our diabetic rats appears to be a result of decreased tubular reabsorption rather than increased filtration of albumin.