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

  1. Janet K. Snell-Bergeon, PHD2
  1. 1Center for Proteomics, Case Western Reserve University, Cleveland, Ohio
  2. 2Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado
  1. Corresponding author: Janet K. Snell-Bergeon, janet.snell-bergeon{at}


OBJECTIVE To define a panel of novel protein biomarkers of renal disease.

RESEARCH DESIGN AND METHODS Adults 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 function 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 to MA by the 6-year visit and 11 control subjects, and four proteins (Tamm-Horsfall glycoprotein, α-1 acid glycoprotein, 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).

RESULTS In the label free analysis, a model of progression to MA was built using 252 peptides, yielding an area under the curve (AUC) of 84.7 ± 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 (odd ratio [OR] 2.9, 95% CI 1.3–6.2, P = 0.008), progranulin (1.9, 0.8–4.5, P = 0.16), clusterin (0.6, 0.3–1.1, P = 0.09), and α-1 acid glycoprotein (1.6, 0.7–3.7, P = 0.27) improved the AUC from 0.841 to 0.889.

CONCLUSIONS A panel of four novel protein biomarkers predicted early renal damage in type 1 diabetes. These findings require further validation in other populations for prediction of renal complications and treatment monitoring.

  • Received August 9, 2011.
  • Accepted November 22, 2011.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.