Author ORCID Identifier
Document Type
Article
Publication Date
3-1-2012
Abstract
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 labelfree proteomic discovery phase was conducted in 13 patientswho progressed toMAby 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 weremeasured by enzymelinked 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 (odds ratio 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.
Language
555
Publication Title
Diabetes Care
Grant
R01HL061753
Rights
© 2012 by the American Diabetes Association. 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 http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
Recommended Citation
Daniela Schlatzer, David M. Maahs, Mark R. Chance, Jean-Eudes Dazard, Xiaolin Li, Fred Hazlett, Marian Rewers, Janet K. Snell-Bergeon; Novel Urinary Protein Biomarkers Predicting the Development of Microalbuminuria and Renal Function Decline in Type 1 Diabetes. Diabetes Care 1 March 2012; 35 (3): 549–555. https://doi.org/10.2337/dc11-1491
Manuscript Version
Final Publisher Version