Biomarkers of rapid chronic kidney disease progression in type 2 diabetes

• DOI: 10.1038/ki.2015.199
• Publication Date: 2015-07-22T15:41:52Z
• Authors: 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
• Keywords: Male; 0301 basic medicine; Time Factors; 610; Kidney; 03 medical and health sciences; Risk Factors; Predictive Value of Tests; 616; Odds Ratio; Humans; Diabetic Nephropathies; Prospective Studies; Renal Insufficiency, Chronic; Aged; Aged, 80 and over; diabetes; Reproducibility of Results; 3. Good health; Logistic Models; Scotland; Diabetes Mellitus, Type 2; ROC Curve; statistics; Area Under Curve; Case-Control Studies; Disease Progression; epidemiology; Female; chronic kidney disease; Biomarkers; Glomerular Filtration Rate

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.