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Abstract
Impaired physical function contributes to falls, fractures, and mortality among patients undergoing dialysis. Using a metabolomic approach, we identified metabolite alterations and effect size-based composite scores for constructs of impaired gait speed and grip strength. 108 participants incident to dialysis had targeted plasma metabolomics via liquid chromatography-mass spectrometry and physical function assessed (i.e., 4 m walk, handgrip strength). Physical function measures were categorized as above/ below median, with grip utilizing sex-based medians. To develop composite scores, metabolites were identified via Wilcoxon uncorrected p < 0.05 and effect size > 0.40. Receiver operating characteristic analyses tested whether scores differentiated between above/below function groups. Participants were 54% male, 77% Black and 53 ± 14 y with dialysis vintage of 101 ± 50 days. 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, composite scores were composed of 22 and 12 metabolites for grip strength and gait speed, respectively. Area under the curve for metabolite composite was 0.88 (gait) and 0.911 (grip). Composite scores of physical function performed better than clinical parameters alone in patients on dialysis. These results provide potential pathways for interventions and needed validation in an independent cohort.
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1 Indiana University School of Medicine, Indianapolis, USA (GRID:grid.257413.6) (ISNI:0000 0001 2287 3919)
2 Indiana University, Department of Biostatistics, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X)
3 Massachusetts General Hospital, Department of Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924)
4 Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623)
5 University of Mississippi Medical Center, Department of Medicine, Jackson, USA (GRID:grid.410721.1) (ISNI:0000 0004 1937 0407)
6 Indiana University School of Medicine, Indianapolis, USA (GRID:grid.257413.6) (ISNI:0000 0001 2287 3919); IUPUI, School of Health and Human Sciences, Indianapolis, USA (GRID:grid.257413.6) (ISNI:0000 0001 2287 3919)