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Abstract: PO2063

Serum and Skeletal Muscle Acylcarnitines And Physical Function in CKD Stage 5-5D

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Moorthi, Ranjani N., Indiana University, Indianapolis, Indiana, United States
  • Cranor, Alissa Ann, Indiana University, Indianapolis, Indiana, United States
  • Swinney, Kimberly, Indiana University, Indianapolis, Indiana, United States
  • Melo ferreira, Ricardo, Indiana University, Indianapolis, Indiana, United States
  • Oconnell, Thomas, Indiana University, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University, Indianapolis, Indiana, United States
  • Avin, Keith G., Indiana University, Indianapolis, Indiana, United States
Background

Sarcopenia is highly prevalent among those with advanced CKD. The metabolite signature of skeletal muscle in patients with CKD is poorly studied. We hypothesized that skeletal muscle metabolites would be different between serum and muscle in those with CKD 5-5D as compared to healthy adults.

Methods

Subjects: 34 subjects participated; 17 with CKD (10 CKD-5, 7 CKD 5D) undergoing renal transplant and 17 healthy donors. All had blood drawn and transversus abdominus muscle biopsy during surgery. Physical Function tests done the week before were: Sit to stand (STS), 6 minute walk test (6MW), 4m gait speed (fast and usual). Metabolomics: Targeted mass spectrometry (MS) was performed on serum and muscle using the Biocrates Absolute IDQ. Differences were tested between those with and without CKD.

Results

There were no differences in age, height, weight or BMI between CKD and healthy subjects. Physical Function: The CKD group had poorer performance for the STS(13 vs 19), 6MW(434 vs 589m), fastest gait speed(1.62 vs 2.00 m/s) and usual gait speed(1.18 vs 1.34m/s), all p<0.05. Metabolomics: The heatmap depicted two distinct signatures in both serum and skeletal muscle between CKD and donors. Serum demonstrated 59 significantly different metabolites, especially in fatty acid metabolism with increases in short and medium chain acylcarnitines C4-C12, and nine hydroxylated and dicarboxylated acylcarnitines in CKD (p<0.05). Lower 6MWT distance was independently associated with levels of C10-14 even after adjusting for CKD status and age in multivariate regression analyses. Skeletal muscle demonstrated significant differences in 42 metabolites, with consistently higher acylcarnitine levels in recipients, including short chain (i.e. C4.1, C5.1, C6.1), long chain and dicarboxyls.

Conclusion

Our data demonstrates patients undergoing renal transplant have increased acylcarnitine levels in serum and muscle that are independently associated with poor physical performance. These results suggest impaired b-oxidation of fatty acid metabolism that affects physical function. Understanding these pathways will allow targeted therapeutics to improve the disabling sarcopenia observed in patients with CKD.

Funding

  • NIDDK Support