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KIDNEY DYSFUNCTION IS ASSOCIATED WITH DIMINISHED SKELETAL MUSCLE MITOCHONDRIAL PLASTICITY IN LIVER TRANSPLANT RECIPIENTS

Abstract

BACKGROUND: Liver transplant (LT) recipients experience severe weight gain after transplant. This weight gain is driven by myopenia and subsequent metabolic inflexibility that culminates in an exacerbated risk of cardiometabolic disease. The risk of cardiovascular disease is increased in LT recipients with impaired kidney function. We do not fully understand the underlying physiological mechanisms that link kidney dysfunction with cardiometabolic disease in this patient population. Therefore, the purpose of this study was to determine the relationship between renal dysfunction and skeletal muscle mitochondrial plasticity in LT patients. We hypothesized that worse kidney function would be associated with impaired skeletal muscle mitochondrial oxidative capacity. METHODS: LT recipients were recruited from Virginia Commonwealth University Health Systems outpatient clinic visits. Venous blood samples were analyzed as part of routine clinical labs including renal function reported as estimated glomerular filtration rate (eGFR) calculated using the race free CKD-EPI equation. Skeletal muscle mitochondrial capacity of the wrist flexor muscle group was determined using near-infrared spectroscopy coupled with repeated, transient arterial occlusions to measure the recovery kinetics of oxygen consumption following an acute bout of handgrip exercise. The metabolic recovery rate constant (Tc) of muscle metabolism was calculated and reported as an index of mitochondrial oxidative capacity. Statistical associations were conducted using Pearson’s correlation test. RESULTS: 21 LT recipients (11 Male/10 Female; 5 African American/1 Asian/15 Caucasian; Mean ± SD: Age 58±9 years; body mass index 36.5±5.9 kg/m2) were enrolled. Renal function measured by eGFR (54±19 mL/min/1.73m2) was negatively associated with skeletal muscle mitochondrial oxidative capacity (Tc: 79.73±26.47 seconds; r = -0.51, p = 0.02). CONCLUSIONS: Impaired kidney function was associated with diminished skeletal muscle mitochondrial oxidative capacity in LT recipients. Future studies are warranted to establish if the observed impairments in mitochondrial plasticity are the mechanistic underpinning of metabolic inflexibility and cardiometabolic sequelae that are increased in LT recipients with impaired kidney function. FUNDING: Supported by NIH UL1TR002649

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