title: Novel urinary protein biomarkers predicting the development of microalbuminuria and renal function decline in type 1 diabetes.
abstract: OBJECTIVE
  To define a panel of novel protein biomarkers of renal disease.
  
  
  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 (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.
authors.affiliation: Center for Proteomics, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schlatzer
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.forename: Mark R
authors.initials: MR
authors.lastname: Chance
authors.forename: Jean-Eudes
authors.initials: JE
authors.lastname: Dazard
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Fred
authors.initials: F
authors.lastname: Hazlett
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000209:etiology / Q000378:metabolism* / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002853:Chromatography, Liquid; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers