Size and charge selectivity of the glomerular filter in patients with insulin-dependent diabetes mellitus: Urinary immunoglobulins and glycosaminoglycans

Background: In diabetic nephropathy, a reduction in negative membrane charg e in the glomerular filter, i.e., the number of sulphated groups of glycosa minoglycans, has been argued to lead to increases in excretion of negativel y charged molecules, such as albumin and IgG4. However, albuminuria and an increased excretion rate of IgG may also be caused by an increase in radius or number of glomerular large pores, Methods: Timed urinary excretion rate s of sulphated glycosaminoglycans, albumin, and IgG2, IgG4, and IgM were an alyzed in 94 patients with insulin-dependent diabetes mellitus with differe nt degrees of nephropathy and compared with the excretion rates in 26 contr ol subjects. Sulphated glycosaminoglycans were measured spectrophotometrica lly after addition of 1,9-dimethylmethylene blue. Albumin and immunoglobuli ns were measured by immunoassays. Results: With increases in the albumin ex cretion rate the excretion of IgG2, IgG4, and IgM also increased, in contra st to a decrease in glycosaminoglycans and the ratio between IgG2 and IgG4 (selectivity index). This index decreased from 6.2 to 0.7 (median; p < 0.01 ), However, with linear regression analysis the excretion rates of albumin and immunoglobulins were not associated with those of glycosaminoglycans. C onclusion: In diabetic nephropathy changes in both large-pore number and in charge selectivity may be pathogenic mechanisms for albuminuria. Copyright (C) 1999 S. Karger AG, Basel.