title: Triphasic changes in selectivity with increasing proteinuria in type 1 and type 2 diabetes.
abstract: 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 less than 30 micrograms 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 greater than 250 micrograms 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.
authors.affiliation: Department of Medicine, Austin Hospital, Heidelberg, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Jerums
authors.forename: T J
authors.initials: TJ
authors.lastname: Allen
authors.forename: M E
authors.initials: ME
authors.lastname: Cooper
mesh_terms: D000419:Albuminuria; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D011507:Proteinuria; D014168:Transferrin / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007074:Immunoglobulin G; D014168:Transferrin