Multiplatform Metabolomic Profiling of the Unilateral Ureteral Obstruction Murine Model of CKD.

Abstract

In chronic kidney disease (CKD) research, animal models such as the unilateral ureteral obstruction (UUO) rodent model are crucial to understanding disease progression, particularly renal fibrosis. Despite its widespread use, the molecular mechanisms driving CKD remain incompletely understood. Given the interplay between metabolism and fibrosis, a comprehensive metabolomic analysis of UUO renal tissue is necessary. This study involved untargeted multiplatform analysis using liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled with mass spectrometry (MS) to examine murine kidney tissue from the UUO model. The results highlight metabolic changes associated with tubulointerstitial fibrosis, which affect pathways such as the tricarboxylic acid (TCA) cycle, the urea cycle, and lipid metabolism. In particular, fibrosis impacts the lipidomic profile, with decreases in most lipid classes and increases in specific glycerophospholipids, hexosylceramides, and cholesterol esters. These findings demonstrate the value of a multiplatform approach in elucidating metabolic alterations in CKD, providing information on the underlying molecular mechanisms and paving the way for further research.