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Biomarkers of rapid chronic kidney disease progression in type 2 diabetes

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Helen C. Looker, Marco Colombo, Sibylle Hess, Mary J. Brosnan, Bassam Farran, 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

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalKidney International
Volume88
Issue number4
Early online date22 Jul 2015
DOIs
Publication statusPublished - Oct 2015

King's Authors

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.

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