Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

作者：Esther Nkuipou‐Kenfack, Flore Duranton, Nathalie Gayrard, Àngel Argilés, Ulrika Lundin, Klaus M. Weinberger, Mohammed Dakna, Christian Delles, William E. Mullen, Holger Husi, Julie Klein, Thomas Koeck, Petra Zürbig, Harald Mischak · 发表于：PLoS ONE · 年份：2014 · DOI：10.1371/journal.pone.0096955 · 被引用次数：112 · 研究领域：Metabolomics and Mass Spectrometry Studies、Chronic Kidney Disease and Diabetes、Dialysis and Renal Disease Management

Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = -0.8031; p<0.0001 and ρ = -0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did re...