#4344 CHANGES IN ENERGY METABOLISM IN THE KIDNEY WITH TUBULOINTERSTITIAL FIBROSIS: AN EX VIVO WHOLE TISSUE 2D-COSY APPROACH

Abstract Background and Aims Tubulointerstitial fibrosis is the common pathological manifestation in chronic kidney disease (CKD) can indicate whether a patient will progress to failure. The metabolic consequences of developing are not well understood. This project aimed investigate changes cortex using an adenine-diet murine model progressive CKD. Method C57Bl/6J mice were treated with adenine-supplemented diet (0.2% adenine) or control for eight weeks. At end treatment, function was assessed (serum creatinine, proteinuria), animals euthanised, kidneys removed. A transverse section prepared histology. Whole cortical tissue analysed two-dimensional correlated spectroscopy (2D-COSY), form proton nuclear magnetic resonance (NMR) spectroscopy. Biochemical species, including metabolites lipids, within identified compared respective histological tubulointerstitial level traditional serum markers function, plasma creatinine blood urea nitrogen. 2D-COSY spectrum be found Figure 1A. Results induced fibrosis, mirrored by increases nitrogen, indicating decreased function. analysis demonstrated numerous parallel increasing levels that detected. Increases belonging glycolysis (D-glucose, glucose-6-phosphate lactate) pentose-phosphate (myo-inositol, D-ribose-5-phosphate, glucuronic acid) pathways observed, as decrease lipid. Additionally, creatine number amino acids also observed. These displayed Table 1 1B. Conclusion primary cell type proximal tubular epithelial cell. Due its unique water solute transport, this has very high demand utilizes fatty acid oxidation source energy. However, when these cells under stress contributes such those present animal disease, dysfunction occurs. We observed significant decreases various lipid signals being utilised instead esterified triglycerides accumulate kidney, causing lipotoxicity. Increased glucose-6-phosphate, lactate D-glucose, increased myo-inositol, D-ribose-5-phosphate indicative utilisation pentose phosphate pathway respectively methods energy metabolism. Here, we provide evidence leads shift used cells. study provides new insights into biochemical occur during development CKD progression.