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Abstract: TH-OR108

Early Clinical Experience with Gene-Edited Porcine Kidneys in Four Human Recipients

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Riella, Leonardo V., Massachusetts General Hospital Department of Medicine, Boston, Massachusetts, United States
  • Palsson, Ragnar, Massachusetts General Hospital Department of Medicine, Boston, Massachusetts, United States
  • Hullekes, Frank E., Massachusetts General Hospital Department of Medicine, Boston, Massachusetts, United States
  • Verhoeff, Rucháma, Massachusetts General Hospital Department of Medicine, Boston, Massachusetts, United States
  • Borges, Thiago J., Massachusetts General Hospital Department of Medicine, Boston, Massachusetts, United States
  • Rosales, Ivy A., Massachusetts General Hospital Department of Pathology, Boston, Massachusetts, United States
  • Avillach, Claire, Massachusetts General Hospital Department of Pathology, Boston, Massachusetts, United States
  • Colvin, Robert B., Massachusetts General Hospital Department of Pathology, Boston, Massachusetts, United States
  • Curtis, Michael, eGenesis, Cambridge, Massachusetts, United States
  • Getchell, Kristen, eGenesis, Cambridge, Massachusetts, United States
  • Kawai, Tatsuo, Massachusetts General Hospital Department of Surgery, Boston, Massachusetts, United States

Group or Team Name

  • MGH Xenotransplant Group
Background

Gene-edited porcine kidney xenotransplantation has entered early clinical application to address kidney failure and organ shortage. However, graft durability, renal complications, and mechanisms of xenograft injury remain undefined. We report clinical outcomes and mechanistic insights from 4 human recipients of gene-edited porcine kidney xenografts.

Methods

Four patients with ESKD underwent transplantation with EGEN-2784 porcine kidneys; all had prolonged wait times and no suitable living donor. Induction immunosuppression included antithymocyte globulin, corticosteroids, anti-CD20 therapy, and complement inhibition, followed by maintenance with anti-CD154 costimulation blockade, tacrolimus, mycophenolic acid, and prednisone. Longitudinal monitoring included creatinine, proteinuria, electrolytes, biopsies, donor kidney endothelial-cell crossmatch assays, multiplex immunofluorescence and pathogen surveillance.

Results

All recipients demonstrated immediate xenograft function with dialysis independence (Fig. 1A). The second recipient maintained xenograft function for 9 months before developing late microvascular/endothelial injury requiring graft explantation, followed by successful human kidney allotransplantation without evidence of sensitization. Early T-cell–mediated rejection occurred in the first two recipients and responded to treatment (Fig. 1B); after modification of the induction regimen, subsequent cases did not develop early cellular rejection. Follow-up of the remaining recipients continues. Persistent proteinuria occurred in two recipients without hypoalbuminemia. Blood pressure, electrolytes, and volume homeostasis were preserved, and no porcine pathogen transmission was detected.

Conclusion

Gene-edited porcine kidneys can provide immediate and sustained renal replacement in humans, including prolonged dialysis-free survival and successful transition to allotransplantation. Microvascular endothelial injury has been a key limitation to durability. Refinement of immunosuppressive and monitoring strategies will be essential to improve durability and advance clinical xenotransplantation.