Time Course of Glycolytic Control Protein Expression in Urinary Extracellular Vesicles (UEV) of Deceased Donor Kidney Transplant Recipients

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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.

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