Abstract
BACKGROUNDMitochondrial dysfunction in patients with chronic kidney disease (CKD) contributes to the development of sarcopenia, central to the frailty phenotype. The impact of exercise on muscle mitochondrial energetics in patients with CKD is unknown.METHODSWe performed an interim analysis of the ESTEEM-VIDA CKD study, a pilot randomized trial of a 12 week, home-based, video-supervised exercise intervention in CKD patients. Vastus lateralis biopsy samples were analyzed by high resolution respirometry (Oroboros O2k) pre and post intervention. Two protocols were run: 1) muscle tissue was homogenized using the PBI Shredder and the O2 consumption and hydrogen peroxide production were measured simultaneously (using Amplex UltraRed) and 2) O2 consumption was measured on permeabilized muscle fibers in a more comprehensive protocol, including measurements with sub-saturating ADP concentrations. We used paired t-tests to test for differences in mitochondrial respiration rates pre and post exercise intervention.RESULTSRespirometry rates were compared pre and post exercise intervention for 11 participants. Protocol 1 demonstrated an increase in succinate supported leak (53% increase, p=0.005) and pyruvate and succinate supported OXPHOS (57% increase, p=0.0114). There was a decrease in hydrogen peroxide production relative to O2 consumption in the succinate supported leak state (20% decrease, p=0.0326). In protocol 2, pyruvate and malate supported OXHPOS with 31.25µM ADP (44% increase, p=0.0435) and 62.5µM ADP (55% increase, p=0.0485) were significantly increased after exercise, while no statistical differences were obeserved between pre and post exercise intervention for OXPHOS with saturating ADP.CONCLUSIONExercise increased leak and OXPHOS respiratory rates measured on skeletal muscle homogenate (protocol 1), but changes in respiratory rates measured on permeabilized fibers with saturating ADP were not evident. The lack of agreement between the protocols may be attributed to greater sample variability between permeabilized fiber bundles, requiring a greater number of samples to detect a change in respiration rates. Further, our data may indicate increased sensitivity to changes in respiration with sub-saturating levels of ADP.