Abstract: SA-OR105
Xenotransplantation and Physiologic Homeostasis: Case Report of a First Living Human Recipient
Session Information
- Late-Breaking Science Orals - 2
October 26, 2024 | Location: Room 6C, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Lee, Sul A, Massachusetts General Hospital, Boston, Massachusetts, United States
- Lafargue, Marie-Camille, Massachusetts General Hospital, Boston, Massachusetts, United States
- Williams, Winfred W., Massachusetts General Hospital, Boston, Massachusetts, United States
- Gilligan, Hannah M., Massachusetts General Hospital, Boston, Massachusetts, United States
- Safa, Kassem, Massachusetts General Hospital, Boston, Massachusetts, United States
- Cohen Bucay, Abraham, Massachusetts General Hospital, Boston, Massachusetts, United States
- Nissaisorakarn, Pitchaphon, Massachusetts General Hospital, Boston, Massachusetts, United States
- Al Jurdi, Ayman, Massachusetts General Hospital, Boston, Massachusetts, United States
- Jüppner, Harald, Massachusetts General Hospital, Boston, Massachusetts, United States
- Low, Susan, eGenesis Inc, Cambridge, Massachusetts, United States
- Curtis, Michael, eGenesis Inc, Cambridge, Massachusetts, United States
- Riella, Leonardo V., Massachusetts General Hospital, Boston, Massachusetts, United States
Group or Team Name
- Mass General Kidney Transplant Team and eGenesis Team
Background
Although kidney transplantation is the preferred treatment for ESKD, organ shortages severely limit timely access to transplants. Pig-to-human xenotransplantation has been proposed to address this issue, but concerns remain about meeting the physiologic needs of a living human and the potential incompatibility between humans and pigs. Here, we present several physiologic aspects of a gene-edited porcine xenograft in the first living human recipient during 51 days of follow-up.
Methods
A 62-year-old male with ESKD due to diabetes on hemodialysis, who was facing ongoing vascular access challenges, had no living donor options and an expected wait time for a deceased donor kidney exceeding 5 years, was selected for xenotransplantation with a 69-gene-edited porcine kidney donor.
Results
Kidney excretory function was assessed by BSA-adjusted 24-hour urine creatinine clearance (CrCl), Cr-based estimated GFR (eGFR), and cystatin C-based eGFR. The xenograft eGFR was 45-55 ml/min/1.73m2 with a strong correlation among Cr- and Cystatin C-based eGFR (r=0.9). The 24-hour urine CrCl was generally higher than Cr-based eGFR by 7-14 ml/min/1.73m2. Despite concerns about inefficient human angiotensinogen activation by pig renin, the recipient maintained hemodynamic stability post-transplantation. To gauge human anti-diuretic hormone compatibility on porcine kidneys, the osmoregulatory function of the xenograft was evaluated. The electrolyte-free water excretion was 0.5-1.5 L/day with fluctuating serum sodium levels within the normal range. The urine osmolality ranged between 220-670 mOsm/kg H2O. No albuminuria or hematuria was observed post-transplantation. The recipient developed hypocalcemia (8.0±0.5 mg/dL) and hyperphosphatemia (6.7±0.7 mg/dL) post-transplantation, possibly in part related to iatrogenic hypoparathyroidism from prior parathyroidectomy (PTH undetectable). Fractional excretion of phosphorus stayed low (<10%) despite elevated intact fibroblast growth factor 23 (FGF-23).
Conclusion
This case report suggests that the xenograft maintained excretory function, hemodynamic stability, and urinary concentrating capacity during follow-up. While lack of PTH may have contributed to hypocalcemia and reduced phosphate excretion, further investigation into the potential incompatibility of human FGF23 on porcine kidneys is needed.