New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis

摘要: BACKGROUND: The reduced glomerular filtration rate in the advanced stages of chronic kidney disease (CKD) leads to plasma accumulation uraemic retention solutes including proteins. It has been hypothesized that these changes may, at least part, be responsible for CKD-associated morbidity and mortality. However, most studies focused on role individual proteins, while a holistic, large-scale, integrative approach may generate significant additional insight. METHODS: In discovery study, we analysed proteome patients with stage 2-3 CKD (n = 14) 5 haemodialysis (HD) 15), using high-resolution LC-MS/MS analysis. Selected results were validated cohort 40 different or without HD, ELISA. RESULTS: Of total 2054 detected 127 displayed lower, 206 higher abundance HD. Molecular pathway analysis confirmed modification known processes involved complications, decreased haemostasis increased inflammation, complement activation vascular damage. In addition, identified increase during progression lysozyme C leucine-rich alpha-2 glycoprotein, two proteins related damage heart failure. High level glycoprotein was associated mortality HD. CONCLUSIONS: This study provides first time comprehensive assessment proteome, contributing new knowledge potential markers CKD. These will serve as basis future investigating relevance molecules