Immunoglobulin subclasses in the urine of control and streptozotocin-induced diabetic rats and their role in the development of diabetic nephropathy.

Fifty-nine streptozotocin-induced diabetic rats, not treated with insulin clearly demonstrated one of two protein excretion patterns based on urinary albumin and IgG excretion rates. 63% (35/59) of the diabetic rats developed significantly elevated albumin excretion rates (incipient proteinuria) when compared to age-matched control animals. This condition progressed to a highly elevated albuminuria and increased IgG excretion (overt proteinuria). Analysis of IgG subclass content in these diabetic proteinuric rat urines showed that there was a selective excretion of IgG2b into the urine at a time that correlated with the onset of overt proteinuria. This IgG subclass comprised approximately 75% of the total IgG excreted during progressive nephropathy (in some animals, 100%) and was unique as it was not the predominant subclass in the serum of this group of animals. The other 37% of the diabetic rats (22/59) did not develop either incipient or overt diabetic nephropathy. In fact, some animals in this group had statistically less albumin and/or IgG in their urine than control rats. The subclass IgG2c was detected sporadically in the urine of these diabetic non-proteinuric rats throughout the chronological study even though it was the IgG subclass that comprised the lowest serum concentration of all four IgG subclasses. In control rats (total of 19), urinary albumin and low levels of the subclass IgG2a were detected throughout the chronological study; both of which increased with the age of the rat. However, in contrast to diabetic rats, the subclasses IgG1 and IgG2b were not detected in the urine of control rats until late in the chronological study.(ABSTRACT TRUNCATED AT 250 WORDS)