TY - JOUR
T1 - New insights into muscle function in chronic kidney disease and metabolic acidosis
AU - Chalupsky, Megan
AU - Goodson, David Alex
AU - Gamboa, Jorge L.
AU - Roshanravan, Baback
N1 - Publisher Copyright:
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
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U2 - 10.1097/MNH.0000000000000700
DO - 10.1097/MNH.0000000000000700
M3 - Article
C2 - 33767065
AN - SCOPUS:85103477878
VL - 30
SP - 369
EP - 376
JO - Current Opinion in Nephrology and Hypertension
JF - Current Opinion in Nephrology and Hypertension
SN - 1062-4821
IS - 3
ER -