Nephrotic-Like Proteinuria in Experimental Diabetes

Aims/Hypothesis: Streptozotocin (STZ) diabetic rats are characterized by the development of albuminuria. It is not known, however, whether the excess excretion of protein is primarily due to intact protein or protein fragments or whether it is specific for albumin or occurs for all high-molecular-weight plasma proteins. To test this we have measured the excretion rates and fractional clearances of [ 14 C]albumin, [ 3 H]immunoglobulin G and [ 3 H]transferrin in diabetic rats. Methods: The radiolabeled proteins were delivered to the circulation of conscious diabetic (STZ induced for 6 weeks) and control rats by ALZET osmotic pumps. The plasma level of the radiolabeled proteins reached steady-state levels by day 7. Urine and plasma samples from day 7 were used to determine the excretion rates of the proteins by radioactivity and radioimmunoassay. Results: When excretion rates were determined by radioactivity it was apparent that only the albumin excretion rate increased significantly with STZ diabetes to a value of 354 ± 166 µg/min which agrees with proteinuria determined by Biuret assay of 299.9 ± 52.4 µg/min. The major proportion of protein being excreted was in the form of protein fragments which are not detected by conventional immmunochemical assays. Conclusion: The previously unrecognized nephrotic-like levels of proteinuria in experimental diabetes appears to be associated with an albumin-specific mechanism responsible for the increase in albumin peptides in urine. There was significant lowering of plasma albumin concentration but plasma concentrations of transferrin and immunoglobulin G remained unchanged. There was also no significant appearance of intact protein in urine that is normally found in nephrotic states.