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Abstract: TH-PO824

Association of Mitochondrial Respiration in Peripheral Blood Mononuclear Cells With Fatigue in Persons With CKD

Session Information

Category: Health Maintenance‚ Nutrition‚ and Metabolism

  • 1400 Health Maintenance‚ Nutrition‚ and Metabolism

Authors

  • Kim, Tae Youn, University of California Davis, Sacramento, California, United States
  • Badhesha, Harshanna, University of California Davis, Sacramento, California, United States
  • Batra, Radhika, University of California Davis, Sacramento, California, United States
  • Gipe, Jesse, University of California Davis, Sacramento, California, United States
  • Ahmadi, Armin, University of California Davis, Sacramento, California, United States
  • Vargas, Chenoa R., University of California Davis, Sacramento, California, United States
  • Norman, Jennifer E., University of California Davis, Sacramento, California, United States
  • Jue, Thomas, University of California Davis, Sacramento, California, United States
  • Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States
  • Gamboa, Jorge, Vanderbilt University, Nashville, Tennessee, United States
  • Roshanravan, Baback, University of California Davis, Sacramento, California, United States
Background

Increased physical frailty and fatigue are prevalent in persons with chronic kidney disease (CKD), contributing to poor quality of life and increased morbidity and mortality risk. Impaired mitochondrial function adversely impacts energy metabolism and may contribute to increased fatigue. While patient-reported fatigue is a complex syndrome involving physiological and psychological mechanisms, little is known about the relevance of PBMC mitochondrial bioenergetics to fatigue in CKD.

Methods

We performed a cross-sectional analysis of the association of PBMC mitochondrial energetics and patient reported fatigue in 27 persons. PBMC basal respiration (BR) and maximal uncoupled respiration (MR) were measured using the high resolution respirometry (Oroboros O2k). Fatigue and depression were measured using the 8-item PROMIS® Fatigue and Depression scales respectively. A higher PROMIS score indicates having more fatigue or depressive mood. Linear regression with robust standard errors was used to test associations adjusting for sex, age, and depression.

Results

Fifty-two percent of the sample were male and diabetes with a mean age of 63±10 years and mean eGFR of 37±12ml/min per 1.73m2. The mean depression and fatigue scores were 47±8.3 and 50±8.5 respectively. The mean PBMC BR and MR were 2.2±0.8 and 9.3±3.3 pmol O2/min/10K cells respectively. Spearman's correlation coefficient was -.43 (p =.025) between BR and fatigue and -.46 (p =.015) between MR and fatigue. The elevated BR was associated with less fatigability after adjustment of sex and age. Each 1 standard deviation greater BR was associated with a 8.7-point (95%CI [-16.0, -1.3], p=.023) reduction in fatigue. Further adjustment for depression minimally attenuated the estimated association (8.5 points, 95%CI [-14.6, -2.4], p=.0008), suggesting a potential role of PBMC mitochondrial energetics in explaining the variation in fatigability.

Conclusion

In a cross-sectional analysis, greater PBMC mitochondrial respiration was associated with improved patient-reported outcomes. Further research is needed to examine longitudinal impact of improving PBMC mitochondrial function on patient outcomes such as fatigue and quality of life in a larger cohort of CKD.

Funding

  • NIDDK Support