Triphasic Changes in Selectivity with Increasing Proteinuria in Type 1 and Type 2 Diabetes

Two indices of the selectivity of proteinuria, the immunoglobulin G (IgG)/albumin and the IgG/transferrin clearance ratios, were studied cross‐sectionally and serially over 7 years in a cohort of 52 Type 1 and 60 Type 2 diabetic patients without established diabetic nephropathy. In Type 1 and Type 2 diabetic patients with albuminuria <30 μg min⁻¹, both protein clearance ratios were significantly higher than in 27 control subjects. As albuminuria increased, there was a decrease in both protein clearance ratios. However, at albumin clearances above 90 nl s⁻¹ equivalent to albumin excretion rates of >250 μg min⁻¹, a positive correlation was found in Type 2 diabetic patients between protein clearance ratios and albuminuria. In individual Type 1 and Type 2 diabetic patients with progressively increasing proteinuria, serial measurements of selectivity showed a decline in both protein clearance ratios with the onset of microalbuminuria. Episodes of transient microalbuminuria were also associated with a fall in the IgG/albumin clearance ratio. The results suggest that the selectivity of proteinuria undergoes a triphasic change with the development of diabetic nephropathy. In the first phase, proteinuria is non‐selective with IgG clearance equal to or exceeding transferrin or albumin clearance. As microalbuminuria develops, there is a progressive increase in selectivity reflecting the preferential excretion of transferrin and albumin compared with IgG. In later stages of nephropathy, as shown in Type 2 diabetic patients with macroalbuminuria, there is a return to non‐selective proteinuria. 1989 Diabetes UK