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Muscle mitochondrial dysfunction at different stages of chronic kidney disease (CKD)
Author(s) -
Gamboa Jorge,
Keller Chad A.,
Falck Aaron M.,
Roshanravan Baback,
Brown Nancy J.,
Ikizler Talat Alp
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.908.2
Subject(s) - kidney disease , medicine , sarcopenia , phosphocreatine , skeletal muscle , mitochondrion , endocrinology , diabetes mellitus , mitophagy , cardiology , biology , energy metabolism , apoptosis , biochemistry , autophagy , microbiology and biotechnology
Sarcopenia and frailty are commonly observed in patients with CKD. Mitochondria, as the principal source of energy, are important for proper muscle function, and may play a role in frailty and sarcopenia. We have previously reported reduced mitochondrial content in patients with CKD on maintenance hemodialysis (MHD) probably due to increased mitophagy. We have also found smaller mitochondria in skeletal muscle of patients on MHD, which may be the consequence of increased mitochondrial fission. We now evaluated the hypothesis that mitochondrial dysfunction is associated with the severity of chronic kidney disease (CKD). For this purpose we evaluated 22 patients on MHD, 20 patients with history of CKD stage 3–5 but not on MHD, and 21 controls with no history of CKD that were matched by gender, history of diabetes, BMI, and race. We measured in vivo mitochondrial function by 31‐phosphorus magnetic resonance spectroscopy ( 31 P‐MRS) in the quadriceps muscle. We used the half time recovery of phosphocreatine (P‐Cr) after a brief exercise as the measure of mitochondrial function. A faster recovery correlates with better mitochondrial function. We also measured physical activity using the six‐minute walk test. Controls and patients on MHD were similar in terms of age (46.9±9.5 vs. 47.7±11.7) but younger compared to patients with CKD stage 3–5 (63.6±9.0). BMI was similar among the groups (30.1±5.9, 30.4±5.2, and 29.6±7.9; controls CKD stage 3–5, and patients on MHD, respectively). We found that the half time recovery of P‐Cr was faster in controls compared to patients on MHD, but similar to patients with CKD stage 3–5 (Figure 1A). We also found that physical activity measured by 6 minute walk test was higher in controls compared to patients with CKD stage 3–5 and patients on MHD (Figure 1B). There was significant negative correlation between physical activity and mitochondrial function (R 2 =0.37, p<0.001). Our data suggest that in vivo mitochondrial function is impaired in patients on MHD but not in patients with CKD stage 3–5 despite a progressive decrease in physical activity among the groups. Further studies are required to evaluate the efficacy of interventions, such as mitochondrial targeted‐therapies or exercise, on mitochondrial function in patients with CKD. Support or Funding Information NIH/NIDDK (K23DK100533) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .