Mr Tyrone Humphries1,2,3, A/Prof GLENDA GOBE1,3, Dr AARON URQUHART1,3, Prof GRAHAM GALLOWAY1,3, A/Prof DAVID VESEY1,2,3, A/Prof ROSS FRANCIS1,2,3
1University Of Queensland, Brisbane, Australia, 2Princess Alexandra Hospital, Woolloongabba, Australia, 3Translational Research Institute, Woolloongabba, Australia
Aim: To investigate pathologically-associated metabolic changes in the kidneys using an adenine-diet chronic kidney disease (CKD) mouse model.
Background: Kidney fibrosis is the common pathological manifestation across CKD aetiologies. Sustained inflammation and fibrosis have been shown to cause a change in preferred energy metabolic pathway in the cells of the kidney.
Methods: Kidney cortical tissue from mice receiving a control or adenine-supplemented diet for four weeks (early inflammation and fibrosis) were analysed by two-dimensional (2D) nuclear magnetic resonance spectroscopy and compared with histology and biomarkers of kidney damage. Tissue metabolite and lipid levels were calculated using Mnova software.
Results: Differences in serum and urine disease markers at this early disease stage were not significant, consistent with the low sensitivity of these clinical markers in early stages of CKD in humans. Early inflammatory and fibrotic histological changes were present in the treatment kidneys. Multivariate statistical analysis of 2D spectra revealed significant decreases in levels of fatty acids (fold change (FC)=-2.37, p<0.05) and isoleucine (FC= 1.54, p<0.05) and increases in levels of phosphorylcholine (FC=2.01, p<0.05) and lactate (FC=1.71, p<0.05) within the treatment kidney cortex compared to control.
Conclusions: Triglyceride accumulation in the kidney is reported in fibrosis from a preferential energy pathway change from fatty acid oxidation towards aerobic and anaerobic glycolysis. Both increased esterification of fatty acids and inhibition of lipolytic enzymes are common with fibrosis and could cause the decrease in free fatty acid levels observed. Increased levels of lactate, coupled with hypoxia that kidney fibrosis introduces, could also be caused by preferential change. This study provides new insight into the changes in biochemical pathways that occur in the kidney during CKD progression.
Biography:
Mr Tyrone Humphries is a PhD candidate at the Faculty of Medicine, University of Queensland. His major research interests include inflammation, fibrosis in CKD and biomarker discovery. His thesis aims to explore magnetic resonance technologies for evaluating progression in chronic kidney disease. Mr Humphries comes from a diverse employment background with roles in the military, academia, clinical trials and in basic science.