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Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.

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Author

  • Helen C Looker
  • Marco Colombo
  • Sibylle Hess
  • Mary J Brosnan
  • Bassam Farran
  • R Neil Dalton
  • Max C Wong
  • Charles Turner
  • Colin N A Palmer
  • Everson Nogoceke
  • Leif Groop
  • Veikko Salomaa
  • David B Dunger
  • Felix Agakov
  • Paul M McKeigue
  • Helen M Colhoun
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Summary, in English

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.Kidney International advance online publication, 22 July 2015; doi:10.1038/ki.2015.199.

Publishing year

2015

Language

English

Pages

888-896

Publication/Series

Kidney International

Volume

88

Issue

4

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Urology and Nephrology

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1523-1755