Novel Urinary Protein Biomarkers Predicting the Development of Microalbuminuria and Renal Function Decline in Type 1 Diabetes
- Daniela Schlatzer, BS1,
- David M. Maahs, MD, PHD2,
- Mark R. Chance, PHD1,
- Jean-Eudes Dazard, PHD1,
- Xiaolin Li, MS1,
- Fred Hazlett, MS1,
- Marian Rewers, MD, PHD2 and
- Janet K. Snell-Bergeon, PHD2⇓
- 1Center for Proteomics, Case Western Reserve University, Cleveland, Ohio
- 2Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado
- Corresponding author: Janet K. Snell-Bergeon, .
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.
- © 2012 by the American Diabetes Association.
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