Abstract: FR-PO0360
Exploring AKI as a Cause of Diaphragm Dysfunction in the Intensive Care Unit
Session Information
- AKI: Mechanisms - Metabolism and Repair
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Budnick, Isadore, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Floyd, Deana, VA Eastern Colorado Health Care System, Aurora, Colorado, United States
- Faubel, Sarah, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Montford, John R., VA Eastern Colorado Health Care System, Aurora, Colorado, United States
Background
Acute kidney injury (AKI) is a risk factor for prolonged mechanical ventilation (MV) but the causes remain incompletely understood. Diaphragm dysfunction causes prolonged MV, but no studies have evaluated AKI as an upstream cause. Animal studies suggest that AKI causes limb muscle dysfunction via upregulation of E3 ubiquitin (Ub) ligases and abnormal branched-chain amino acid (BCAA) metabolism. These may represent mechanisms of AKI induced diaphragm dysfunction. Herein, we examined molecular changes in diaphragm after murine AKI.
Methods
C57BL/6 male wildtype mice had bilateral ischemia/reperfusion AKI (iAKI) with 26 minutes of renal pedicle clamping or Sham surgery without pedicle clamping. Mice were euthanized after 24 hours. Whole blood was collected and diaphragms were excised. Blood urea nitrogen (BUN) measured with QuantiChrom Urea Assay Kit. Diaphragm homogenized and total RNA was extracted. FBXO32, TRIM63, and BCAT2 qPCR normalized to GAPDH. n = 8 (iAKI) and n = 6 (Sham).
Results
iAKI mice had significantly increased BUN as compared to Sham (Fig A). iAKI mice showed significantly increased expression of TRIM63 and FBXO32 in the diaphragm (Fig B-C). BCAT2 was similar between groups (Fig D). BUN had a significant correlation with FBXO32 but not TRIM63 (Fig E-F).
Conclusion
This is the first known study of molecular changes in the diaphragm after murine AKI. TRIM63 and FBXO32, E3 Ub ligases critical to muscle wasting in other acute conditions (e.g., sepsis), were both increased. Although our group and others have found that BCAA levels are decreased in limb muscle after iAKI, we found that BCAT2, an enzyme that catabolizes BCAA, was not increased in iAKI. We will next analyze additional targets related to BCAA catabolism, Ub mediated protein degradation, and assess diaphragm contractility.
Funding
- Other NIH Support