Abstract: FR-OR068
ESRD Patient-Derived Immune Cells Direct Lymphatic Remodeling and Modulate Response to Kidney Injury
Session Information
- Transplantation: Basic Science Innovations and Advances
November 07, 2025 | Location: Room 370A, Convention Center
Abstract Time: 05:10 PM - 05:20 PM
Category: Transplantation
- 2101 Transplantation: Basic
Authors
- Liu, Jing, Vanderbilt University Medical Center, Nashville, United States
- Khan, Mohd Mabood, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Dilaver, Ragibe Gulsah, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Shelton, Elaine L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kirabo, Annet, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
End-stage renal disease(ESRD)causes profound immune dysregulation,but the impact of the altered immune state on kidney lymphatic function remains poorly understood.Lymphatic vessels have a vital role in maintaining interstitial fluid homeostasis and facilitating the clearance of macromolecules and immune cells following tissue injury.We hypothesized that immune cells of ESRD patients influence lymphatic remodeling and function after kidney injury,thereby contributing to the progression of renal damage.
Methods
Immunodeficient rats(IDRs)were subjected to puromycin aminonucleoside (PAN)-induced nephropathy then reconstituted with peripheral blood mononuclear cells(PBMCs; 30 million; IV)from either ESRD patients or healthy donors. Renal injury and lymphatic remodeling were assessed by albumin-to-creatinine ratio(ACR),Kim1 immunostaining, and quantification of lymphatic vessel density. In vitro, primary human lymphatic endothelial cells(hLECs)were exposed to PBMC-conditioned media or serum from ESRD patients. Markers of lymphatic activation(Prox1, VEGFR3), proliferation(Ki67), and inflammation(TNFα) were evaluated.
Results
Rats reconstituted with ESRD-derived PBMCs exhibited significantly higher ACR and increased Kim1–positive tubular injury compared to controls. These rats also demonstrated increased renal lymphatic vessel density. Notably, the number of kidney-infiltrating dendritic cells positively correlated with lymphatic vessel abundance. In vitro, hLECs exposed to ESRD PBMC-conditioned media showed upregulation of Prox1,VEGFR3, and Ki67,indicating enhanced lymphatic activation and proliferation. Tube formation assays confirmed that both ESRD PBMC supernatants and patient serum stimulated lymphatic network formation. Additionally, TNFα expression was significantly elevated, suggesting an inflammatory lymphatic endothelial phenotype.
Conclusion
This study provides the first evidence that PBMCs from ESRD patients actively modulate lymphatic remodeling in the kidney, promoting an inflammatory form of lymphangiogenesis. These findings reveal a previously unrecognized interaction between the immune system and the renal lymphatic vasculature in ESRD and suggest that targeting lymphatic activation may offer a novel therapeutic approach in the management of progressive chronic kidney disease.
Funding
- NIDDK Support