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Kidney Week

Abstract: FR-PO0361

Metabolomic Profile of Muscle Wasting in Critically Ill Patients with AKI Receiving CRRT

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Nombera-Aznaran, Natalia R., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Wilson, Landon Shay, Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Barnes, Stephen, Targeted Metabolomics and Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Chen, Jin, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Gamboa, Jorge, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Tolwani, Ashita J., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Gonzalez-Seguel, Felipe, University of Kentucky, Lexington, Kentucky, United States
  • Sawaya, Peter, University of Kentucky, Lexington, Kentucky, United States
  • Teixeira, J. Pedro, The University of New Mexico, Albuquerque, New Mexico, United States
  • Mayer, Kirby, University of Kentucky, Lexington, Kentucky, United States
  • Neyra, Javier A., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

Patients with AKI on CRRT experience significant muscle loss during the first week of CRRT and are at high risk of developing intensive care unit-acquired weakness (ICU-AW). However, the underlying metabolic mechanisms of these associations remain unclear.

Methods

We conducted a prospective observational study of critically ill adults with AKI requiring CRRT at two U.S. academic centers. Plasma and effluent samples were obtained within 48 hours and on day 3 after CRRT initiation. Rectus femoris muscle thickness (mT) and echointensity (ei) were assessed by standardized bedside ultrasound, and strength was measured at hospital discharge using the Medical Research Council sum score (MRC-SS), with ICU-AW defined as MRC-SS <48. Non-targeted metabolomics was performed using liquid chromatography–mass spectrometry (SCIEX 7600 + ZenoTOF). Samples were extracted using a modified Bligh–Dyer protocol and processed in MS-DIAL. Metabolite-muscle associations were tested by generalized estimated equations at q<0.05. Signficant metabolites were then compared by ICU-AW status using Mann–Whitney U test (p<0.05). Pathway enrichment was performed in MetaboAnalyst.

Results

16 participants were included (median age 53; 37.5% female; median CCI 3; median SOFA score at enrollment 9). ICU-AW was diagnosed in 11 patients at discharge. Multiple metabolites were significantly associated with longitudinal changes in mT and ei, with distinct matrix-specific signatures (Figure 1). Although ICU-AW group comparisons did not reach statistical significance, several metabolites showed consistent directional trends over time. Pathway analyses highlighted relationships between muscle metrics and D-amino acid and tryptophan metabolism, as well as primary bile acid and arginine biosynthesis.

Conclusion

Paired plasma and effluent metabolomics identified several metabolic features associated with ultrasound-detected muscle trajectories during CRRT, suggesting candidate pathways for future studies aimed at reducing muscle dysfunction in this high-risk population.

Funding

  • NIDDK Support