MO045MITOCHONDRIAL DYSFUNCTION AND MUSCLE ENERGETICS IN CKD PATIENTS. (6th June 2020)

• Record Type: Journal Article
• Authors: Gamboa, Jorge; Ikizler, Alp; Yu, Chang; Damon, Bruce; Brown, Nancy; Towse, Theodore
• Is Part Of: Nephrology dialysis transplantation. Volume 35(2020)Supplement 3
• Publication Date: 2020-06-06
• Subjects: Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfaa140.MO045
• Languages: English
• ISSNs: 0931-0509

Abstract

Abstract: Background and Aims: Patients with chronic kidney disease (CKD) suffer from frailty and sarcopenia. Skeletal muscle mitochondria are important for physical function and could be a target to prevent frailty and sarcopenia. Method: We tested the hypothesis that mitochondrial function worsens with the progression of CKD. We evaluated the interaction between mitochondrial function and co-existing comorbidities such as impaired physical performance, intermuscular adipose tissue (IMAT) infiltration, inflammation, and oxidative stress. We evaluated in-vivo thigh mitochondrial function using 31-phosphorus magnetic resonance spectroscopy to obtain the phosphocreatine (PCr) recovery constant, a measure of mitochondrial function. We measured physical performance using the six-minute walk test, IMAT infiltration and markers of inflammation in plasma. Results: Sixty-three participants were studied including controls (n=21), patients with CKD not on maintenance hemodialysis (MHD; n=20), and patients on MHD (n=22). We found a prolonged PCr recovery constant in patients on MHD (53.3 (43.4, 70.1) seconds) and with CKD not on MHD (46.3 (40, 0, 49.9) seconds) compared to controls (34.2 (28.8, 43.7) seconds) (p<0.001 between groups), Figure 1A-C . Mitochondrial dysfunction was associated with poor physical performance, greater IMAT, and increased markers of inflammation Figure 2A-C . Conclusion: Mitochondrial function worsens with the progression of CKD and correlates with physical function, IMAT, inflammation, and oxidative stress. These data suggest that therapeutic approaches targeted at mitochondrial dysfunction and dynamics could prevent or treat frailty and sarcopenia in patients CKD.