Novel Urinary Protein Biomarkers Predicting the Development of Microalbuminuria and Renal Function Decline in Type 1 Diabetes

OBJECTIVEdTo define a panel of novel protein biomarkers of renal disease. RESEARCH DESIGN AND METHODSdAdults with type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study who were initially free of renal complications (n = 465) were followed for development of micro- or macroalbuminuria (MA) and early renal func-tion decline (ERFD, annual decline in estimated glomerular filtration rate of$3.3%). The label-free proteomic discovery phase was conducted in 13 patients who progressed toMA by the 6-year visit and 11 control subjects, and four proteins (Tamm-Horsfall glycoprotein, a-1 acid glyco-protein, clusterin, and progranulin) identified in the discovery phase were measured by enzyme-linked immunosorbent assay in 74 subjects: group A, normal renal function (n = 35); group B, ERFD without MA (n = 15); group C, MA without ERFD (n = 16); and group D, both ERFD and MA (n = 8). RESULTSdIn the label-free analysis, a model of progression to MA was built using 252 peptides, yielding an area under the curve (AUC) of 84.76 5.3%. In the validation study, ordinal logistic regression was used to predict development of ERFD, MA, or both. A panel including Tamm-Horsfall glycoprotein (odds ratio 2.9, 95 % CI 1.3–6.2, P = 0.008), progranulin (1.9, 0.8