New insights into muscle function in chronic kidney disease and metabolic acidosis

Abstract

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.

Paeoniflorin Ameliorates Skeletal Muscle Atrophy in Chronic Kidney Disease via AMPK/SIRT1/PGC-1α-Mediated Oxidative Stress and Mitochondrial Dysfunction

“…It has been shown that structural changes involving mitochondrial dynamics may result in mitochondrial dysfunction, thereby leading to CKD ( Chalupsky et al, 2021 ). Hence, the balance of mitochondrial dynamics is essential for skeletal muscle and myoblasts.…”

“…Numerous researchers have reported that inflammation, oxidative stress and subsequent mitochondrial dysfunction are important processes in the maintenance of skeletal muscle function in CKD ( Watanabe et al, 2019 ; Chalupsky et al, 2021 ). The excessive accumulation of ROS has been proven to be an important link that leads to oxidative stress and mitochondrial dysfunction in CKD skeletal muscle atrophy ( Abrigo et al, 2018 ).…”

Prevalence and determinants of sarcopenia in Indian patients with chronic kidney disease stage 3 & 4

“…Those with sarcopenia were found to have a greater degree of metabolic acidosis. Metabolic acidosis induces insulin resistance, enhances mitochondrial stress, and activates multiple downstream cytokine mediators, leading to enhanced muscle catabolism [ 23 , 24 ]. Correction of metabolic acidosis was associated with better preservation of total muscle mass [ 8 ].…”

Sarcopenia and sarcopenic obesity in chronic kidney disease: update on prevalence, outcomes, risk factors and nutrition treatment

“…These metabolic events result in decreased cell growth and differentiation in skeletal muscle and consequently higher protein breakdown and lower synthesis. Inhibition of protein synthesis and stimulation of proteolysis contribute to impaired muscle function, muscle wasting, poor physical performance and decline in functional status [3,41 ▪▪ ,42 ▪ ,45,47,48 ▪ ,49–51].…”