Size and Charge Selectivity of the Glomerular Filter in Patients with Insulin-Dependent Diabetes mellitus: Urinary Immunoglobulins and Glycosaminoglycans

Abstract

Background: In diabetic nephropathy, a reduction in negative membrane charge in the glomerular filter, i.e., the number of sulphated groups of glycosaminoglycans, has been argued to lead to increases in excretion of negatively 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 rates of sulphated glycosaminoglycans, albumin, and IgG2, IgG4, and IgM were analyzed in 94 patients with insulin-dependent diabetes mellitus with different degrees of nephropathy and compared with the excretion rates in 26 control subjects. Sulphated glycosaminoglycans were measured spectrophotometrically after addition of 1,9-dimethylmethylene blue. Albumin and immunoglobulins were measured by immunoassays. Results: With increases in the albumin excretion rate the excretion of IgG2, IgG4, and IgM also increased, in contrast 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. Conclusion: In diabetic nephropathy changes in both large-pore number and in charge selectivity may be pathogenic mechanisms for albuminuria.