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Purpose of review : Sarcopenia, defined as decreased muscle mass or function, is prevalent in chronic kidney disease (CKD) increasing the risk of mobility impairment and frailty. CKD leads to metabolic acidosis (MA) and retention of uremic toxins contributing to insulin resistance and impaired muscle mitochondrial energetics. Here we focus on the central role of muscle mitochondrial metabolism in muscle function. Recent findings : Mitochondrial dysfunction underlies muscle wasting and poor physical endurance in CKD. Uremic toxins accumulate in muscle disrupting mitochondrial respiration and enzymes. Changes in mitochondrial quantity, quality, and oxidative capacity contribute to mobility impairment in CKD. Major determinants of muscle mitochondrial function are kidney function, inflammation, and oxidative stress. In CKD, MA is the major determinant of muscle mitochondrial function. Metabolomics reveals defects in pathways linked to mitochondrial energy metabolism and acid-base homeostasis underlying insulin resistance in CKD. Summary : Decreased mitochondrial capacity and quality control can impair muscle function contributing to decreased physical endurance. MA augments insulin resistance perpetuating the catabolic state underlying muscle wasting in CKD. Further studies are needed to investigate if targeting of MA improves muscle mitochondrial function and insulin resistance translating into meaningful improvements in physical endurance.

Background and Objective Chronic kidney disease (CKD) is associated with loss of muscle quality leading to mobility limitation and decreased independence. Identifying predictors of gait speed decline may help target rehabilitative therapies to those at highest risk of mobility impairment. Design, setting and participants, and measurements The current prospective cohort study recruited ambulatory patients with stage 1-4 CKD (eGFR 15-89 ml/min/1.73m2) from nephrology clinics. Predictors included demographic and clinical variables including GFR estimated using serum cystatin C. Outcomes were average change in gait speed (m/s) per year and inclusion in the top tertile of gait speed decline over 3 years. Linear mixed models and relative risk regression were used to estimate associations with annual gait speed changes and fastest tertile of decline. Results Among 213 participants, 81% were male, 22% were black and 43% had diabetes. Mean age was 57 years, median follow-up 3.15 years, mean baseline eGFRcysc 47.9 ml/min/1.73 m2, and median baseline gait speed 0.95m/s [IQR 0.81, 1.10]. Lower baseline eGFRcysc was associated with more rapid loss of gait speed (-0.029 m/s/year [95% CI -0.042, -0.015] per 30 ml/min/1.73 m2 lower eGFR; p<0.001). Diabetes was associated with -0.024m/s/year faster change (95% CI -0.042, -0.007; p=.007). Lower eGFRcysc was associated with a 49% greater risk of rapid gait speed decline (IRR 1.49; 95% CI 1.11, 2.00, p=.008) after adjustment. Prevalent cardiovascular disease and African American race were associated with a 45% greater (IRR 1.45; 95% CI 1.04, 2.01, p=.03) and 58% greater rate of rapid gait speed decline (IRR 1.58; 95% CI 1.09, 2.29, p=.02), respectively. Conclusions Among ambulatory, disability-free patients with CKD, lower eGFRcysc and diabetes status were associated with faster gait speed decline. Lower eGFRcysc, cardiovascular disease, and African American race were associated with rapid gait speed decline.

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