Early clinical experience with gene-edited porcine kidney xenotransplantation in four living human recipients
The Inaugural Richard Slayman International Workshop on Xenotransplantation Click to watch
📄 Advancing Hope Through Science: The Inaugural Richard Slayman International Workshop on Xenotransplantation
Meeting Report – Published in Transplantation (February 2026)
This landmark workshop brought together more than 140 participants from North America, Europe, and Asia to examine the latest advances—and the remaining challenges—in translating xenotransplantation from bench to bedside.
Framed by the legacy of Richard Slayman, the first living recipient of a genetically edited pig kidney, this conversation explores how patient courage, scientific collaboration, and careful clinical design are helping move the field from possibility toward reality.
The episode highlights:
🔹 Why patient selection is critical in early xenotransplantation trials
🔹 How genetic editing is helping overcome immune incompatibility
🔹 The evolving role of immunosuppression, including complement inhibition and CD154 blockade
🔹 New molecular tools for immune and infectious surveillance
🔹 The importance of transparency, ethics, and global collaboration
🔹 What the next 5–10 years may look like for kidney xenotransplantation
This discussion offers an important look at one of the most promising and complex frontiers in transplantation—where innovation, safety, and patient-centered care must advance together.
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Abstract
Introduction: Kidney xenotransplantation using gene-edited porcine organs has entered early clinical application. Initial human experience demonstrates feasibility, yet durability of function and mechanisms of graft injury remain incompletely defined. We report clinical outcomes and mechanistic insights from four living human recipients of kidney xenotransplants.
Methods: Four patients with end-stage kidney disease, prolonged anticipated wait times, and no suitable living donor underwent transplantation with EGEN-2784 kidneys. Immunosuppression induction included antithymocyte globulin, corticosteroids, anti-CD20 therapy, and complement inhibition, followed by maintenance with anti-CD154 monoclonal antibody, tacrolimus, mycophenolic acid, and prednisone. Serial monitoring included kidney function, biopsies, donor kidney endothelial-cell crossmatch assays, multiplex immunofluorescence, and metagenomic pathogen surveillance.
Results: All recipients demonstrated immediate graft function, with rapid normalization of serum creatinine. Electrolyte and volume homeostasis, including potassium and fluid balance, were well maintained. The longest surviving xenograft to date provided dialysis-free function for more than nine months. The first two recipients developed early T-cell–mediated rejection within two weeks, and both episodes responded promptly to treatment with recovery of graft function. After modification of the induction regimen, subsequent recipients did not develop early cellular rejection. Across cases, graft injury showed convergent microvascular and endothelial phenotypes. One recipient developed late graft dysfunction after reduction of immunosuppression, with progressive microvascular injury and thrombotic microangiopathy leading to graft failure and explantation. This patient subsequently underwent successful human kidney transplantation without evidence of anti-HLA sensitization. In another recipient, early graft injury was detected by interferon-γ–stimulated donor kidney endothelial crossmatch despite negative standard testing. This recipient responded to treatment, although microvascular injury with features of TMA persisted. The fourth recipient continues with stable graft function under ongoing clinical follow-up. Persistent proteinuria developed in two of four recipients without clinically significant hypoalbuminemia. No evidence of zoonotic infection or clinically significant arrhythmias was observed.
Conclusion: Gene-edited porcine kidneys can provide immediate and sustained renal replacement in humans, establishing clinical feasibility. However, microvascular and endothelial injury remains the principal barrier to durable graft survival. These processes appear multifactorial, involving innate immune activation and endothelial stress, and may occur in the absence of detectable circulating antibodies. These findings define a distinct biology of xenograft injury, highlighting the need for xenotransplant-specific monitoring and therapeutic strategies.