PR002262 (Project)

Description:In chronic kidney disease (CKD) research, animal models provide invaluable insights into the disease’s etiopathogenesis and progression, particularly through the evaluation of renal tissue. The unilateral ureteral obstruction (UUO) rodent model stands out for its widespread use in CKD studies, due to its advantages to generate renal fibrosis and accelerated mimicry of obstructive nephropathy in humans. Despite its extensive use, the molecular underpinnings driving kidney disease progression remain incompletely understood. Given the crucial interplay between metabolism and fibrosis in CKD, a thorough examination of the UUO renal tissue through metabolomics is required. Untargeted multiplatform analysis enables a comprehensive measurement of the sample metabolic profile, ensuring a maximum coverage of metabolite diversity to yield extensive insights into the metabolism of this renal injury model. Therefore, in this study, murine kidney tissue from the UUO model underwent analysis using three separation techniques—liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE)—coupled with mass spectrometry (MS). The findings reveal metabolic changes associated with tubulointerstitial fibrosis, impacting essential pathways such as the TCA cycle, urea cycle, polyamine metabolism, amino acids, one-carbon metabolism, purine catabolism, and NAD+ synthesis, among others. Furthermore, fibrosis significantly influences the renal tissue's lipidomic profile, characterized by a general decrease in most lipid classes and an increase in glycerophospholipids with ether substituents, hexosylceramides, and cholesterol esters compared to the control. These results underscore the relevance of the untargeted multiplatform approach to obtain a comprehensive overview of the alterations within the renal metabolic map, paving the way for further exploration of the molecular mechanisms underlying CKD.