title: Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.
abstract: Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.
authors.affiliation: Population Health Sciences, University of Dundee, Dundee, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Looker
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Colombo
authors.affiliation: R&D Metabolism and PK Germany, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Hess
authors.affiliation: Pfizer Worldwide Research and Development, Pfizer, Groton, Connecticut, USA.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Brosnan
authors.affiliation: Population Health Sciences, University of Dundee, Dundee, UK.
authors.forename: Bassam
authors.initials: B
authors.lastname: Farran
authors.affiliation: WellChild Laboratory, Kings College, London, UK.
authors.forename: R Neil
authors.initials: RN
authors.lastname: Dalton
authors.affiliation: University Department of Paediatrics, Cambridge University, Cambridge, UK.
authors.forename: Max C
authors.initials: MC
authors.lastname: Wong
authors.affiliation: WellChild Laboratory, Kings College, London, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Turner
authors.affiliation: Medical Research Institute, University of Dundee, Dundee, UK.
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.affiliation: Cardiovascular and Metabolism Disease Therapeutic Area, F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Everson
authors.initials: E
authors.lastname: Nogoceke
authors.affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malmo, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: Department of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: University Department of Paediatrics, Cambridge University, Cambridge, UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.|Pharmatics Limited, Edinburgh, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Agakov
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKeigue
authors.affiliation: Population Health Sciences, University of Dundee, Dundee, UK.|Department of Public Health, NHS Fife, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D015203:Reproducibility of Results; D012307:Risk Factors; D012606:Scotland; D013997:Time Factors
chemical_list: D015415:Biomarkers