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A Panel of Novel Biomarkers Representing Different Disease Pathways Improves Prediction of Renal Function Decline in Type 2 Diabetes
Authors:Michelle J Pena  Andreas Heinzel  Georg Heinze  Alaa Alkhalaf  Stephan J L Bakker  Tri Q Nguyen  Roel Goldschmeding  Henk J G Bilo  Paul Perco  Bernd Mayer  Dick de Zeeuw  Hiddo J Lambers Heerspink
Abstract:ObjectiveWe aimed to identify a novel panel of biomarkers predicting renal function decline in type 2 diabetes, using biomarkers representing different disease pathways speculated to contribute to the progression of diabetic nephropathy.ResultsPatients’ average age was 63.5 years and baseline eGFR was 77.9 mL/min/1.73m2. The average rate of eGFR decline was -2.0 ± 4.7 mL/min/1.73m2/year. When modeled on top of established risk markers, the biomarker panel including matrix metallopeptidases, tyrosine kinase, podocin, CTGF, TNF-receptor-1, sclerostin, CCL2, YKL-40, and NT-proCNP improved the explained variability of eGFR decline (R2 increase from 37.7% to 54.6%; p=0.018) and improved prediction of accelerated eGFR decline (C-index increase from 0.835 to 0.896; p=0.008).ConclusionsA novel panel of biomarkers representing different pathways of renal disease progression including inflammation, fibrosis, angiogenesis, and endothelial function improved prediction of eGFR decline on top of established risk markers in type 2 diabetes. These results need to be confirmed in a large prospective cohort.
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