Chronic kidney disease (CKD) leads to the retention of uremic solutes that disrupt skeletal muscle function1 leading to reduced physical performance and mobility limitation2. Disruption of muscle mitochondrial energetics in CKD may precede the onset of detectable functional limitations. In particular, reduced coupling of ATP production to oxygen consumption (P/O ratio) within mitochondria of skeletal muscle indicates oxidative stress, impaired metabolism, and reduced exercise efficiency3–6. Comprehensive analysis of skeletal muscle mitochondrial energetics in CKD patients has been limited by lack of precise, real-time, non-invasive techniques.

We used in vivo magnetic resonance spectroscopy and optical spectroscopy (31P MRS/OS) procedures to measure resting mitochondrial energetics for the first time among non-diabetic CKD patients (GFR< 60ml/min/1.73 m2). Mitochondrial function parameters were measured according to published protocols7 (Supplemental methods). We compared these measures with results from a reference population of healthy community dwelling adults free of mobility limitation, known kidney and cardiovascular comorbidity (Supplemental Table 1). Briefly, MRS and separate OS measurements were performed during an initial resting state followed by a period of reversible ischemia to separate oxygen uptake from ATPflux. The first dorsal interosseus muscle (FDI) of the hand was selected because it contains well