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Abstract: TH-PO811

Plasma Metabolites and Physical Function in Patients Undergoing Dialysis

Session Information

Category: Health Maintenance‚ Nutrition‚ and Metabolism

  • 1400 Health Maintenance‚ Nutrition‚ and Metabolism

Authors

  • Avin, Keith G., Indiana University Purdue University Indianapolis, Indianapolis, Indiana, United States
  • Moorthi, Ranjani N., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Oconnell, Thomas, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Dickinson, Stephanie, Indiana University Bloomington, Bloomington, Indiana, United States
  • Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Clish, Clary B., Broad Institute, Cambridge, Massachusetts, United States
  • Shafi, Tariq, University of Mississippi School of Medicine, Jackson, Mississippi, United States
  • Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and composite scores associated with measures of impaired physical function (gait speed and grip strength).

Methods

In 108 subjects incident to dialysis, targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function (i.e., 4m walk, handgrip strength) were measured. Gait speed and grip strength were categorized as above/ below median, with grip utilizing sex-based medians. Metabolites significant between gait speed and grip strength groups (Wilcoxon p<0.05) and effect sizes >0.40 were used to develop composite scores. Receiver operating characteristic analyses tested whether scores differentiated between high and low function groups.

Results

Participants were 54% male, 77.4% Black and 53.4 ± 13.9 y. Median (IQR) grip strength was 35.5 (11.1) kg (males) and 20 (8.4) kg (females); median gait speed was 0.82 (0.34) m/s. Of 246 measured metabolites, 30 and 20 metabolites were different between grip strength and gait speed groups respectively with three common metabolites (C7 carnitine, phosphocholine isomer, valine). Composite scores were composed of 22 and 12 metabolites that differentiated grip strength and gait speed, respectively. Area under the curve for metabolite composite was 0.88 (gait) and 0.911 (grip).

Conclusion

n this study, we developed a composite score that represents physical function with metabolites unique for each measure of gait speed and grip strength in patients who are incident to dialysis. We included 22 key metabolites for grip strength and 12 metabolites for gait speed in the composite score, with alterations in fatty acid oxidation and protein synthesis observed in both measures. Given the complexity of the systems involved in physical function, the use of panels of metabolites associated with physical function offers a fresh opportunity to both predict changes over time and offer insight into pathophysiology for those with CKD.

Funding

  • NIDDK Support