IMMUNE COMPLEXES AND THE DEVELOPMENT OF DIABETIC NEPHROPATHY IN UNTREATED AND INSULIN-TREATED DIABETIC SYRIAN HAMSTERS (ALBUMINURIA, PROTEINURIA, IMMUNOGLOBULIN-G)

The role of the immune system in the pathogenesis of late complications associated with diabetes mellitus is controversial. The objective of this study was to determine if immune complexes (IC) are associated with the development of diabetic nephropathy in streptozotocin-induced diabetic Syrian hamsters. Immune complexes were pecipitated from hamster sera with equine rheumatoid-Clq factor, and the IC and serum IgG were quantitated by rocket immunoelectrophoresis. Diabetic hamsters expressed a unique IgG subclass that was detected in the IC and also in the serum. The IC were detected at three distinct times. The first occurrence of IC coincided with the detection of circulating pancreatic antibodies. The significance of the second and third IC occurrences is unknown. Serum IgG levels were elevated in diabetic hamsters when compared to control normal levels. Albumin and IgG concentrations in hamster urine were quantitated by specific radioimmunoassays. Significantly elevated albumin and IgG levels in the urine were used to define the onset of overt proteinuria, a characteristic of diabetic nephropathy. The excretion of urinary proteins was increased in hamsters within one month of diabetes and overt proteinuria developed in all diabetic hamsters by week 20. Even though IC were detected during this time, they were not statistically correlated with the development of overt proteinuria. Initiation of insulin treatment of hamsters for various intervals during the duration of diabetes decreased urine volume, serum glucose, IgG and IC levels. Despite insulin treatment, IC and the unique IgG subclass were detected in the serum of some diabetic hamsters. Albuminuria and IgG proteinuria were controlled by insulin treatment early in the course of diabetes. If diabetic hamsters were uncontrolled for 13 weeks or longer prior to unsulin treatment, control of the proteinuria became increasingly difficult which may indicate the development of an irreversible stage of overt proteinuria. When insulin therapy was stopped after 26 weeks of diabetes, the hamsters redeveloped the manifestations of diabetes within two weeks. Immune complexes and overt proteinuria were detected in all surviving diabetic hamsters after insulin therapy was stopped which indicates an association of IC with the later stages of nephropathy rather than its onset.