Abstract: TH-PO800
Time Course of Glycolytic Control Protein Expression in Urinary Extracellular Vesicles (UEV) of Deceased Donor Kidney Transplant Recipients
Session Information
- Transplantation: Clinical - 2
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Leung, Po Yee Mia, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
- Graver, Alison S., Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
- Katerelos, Marina, Department of Nephrology, Austin Health, Melbourne, Victoria, Australia
- Whitlam, John B., Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
- Power, David A., Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
- Mount, Peter F., Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
Background
An important switch to increased glycolysis has been demonstrated in experimental ischaemia-reperfusion injury. We aimed to measure expression of glycolytic control proteins contained in UEV as a marker for changes in renal glycolysis following deceased donor kidney transplantation.
Methods
In this prospective observational study, urine samples were collected from deceased donor kidney transplant recipients prior to (T0) and after transplant at days 1-3 (T1), 5-10 (T2) and 70-100 (T3). UEV were separated by differential ultracentrifugation and characterized by expression of CD9, TSG101 and THP. Proteins were analysed by immunoblotting and included PFK-L, PFKFB2, pSer483-PFKFB2, PFKFB3, PFKFB4, PK-LR, PK-M2 and NGAL. Densitometry was normalized to urine creatinine, then compared via repeated measures one-way ANOVA.
Results
29 urine samples from 8 subjects were included. Three were anuric at T0. PFK-L was not detected. There were no statistically significant changes in expression of PFKFB2, pSer483-PFKFB2, PFKFB3, PFKFB4 and PK-M2 over time. Expression of PFKFB2 and PK-M2, however, was seen in 8/8 subjects at T1 and persisted in 7/8 subjects at T3. PK-LR was detected in 4/5 samples at T0 and not thereafter (p=0.0010). NGAL was detected in 4/5 subjects at T0 and in 8/8 at T1-3, with expression measured by densitometry reducing over time (p=0.043).
Conclusion
Regulation of glycolytic control in the early post-transplant period is poorly understood. We identified changes in PFKFB2 and PK-M2 immediately post-transplant, which persists over time. PFKFB2 and PK-M2 have been associated with increased glycolysis, including aerobic glycolysis. Future studies will focus on the way this can be used to monitor kidney transplants.