Xenotransplantation and Physiologic Homeostasis: Case Report of a First Living Human Recipient

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.