A genetically modified pig’s kidney kept a 66-year-old man with end-stage kidney failure free of dialysis for a record nine months before he successfully received a human kidney, according to a study published in The Lancet.
Kidney transplantation provides the best survival and quality of life for patients with end-stage kidney disease, but the demand for the organ far exceeds supply. The kidney came from a Yucatan miniature pig and was genetically engineered to be compatible with the human immune system. The transplantation took place at the Massachusetts General Hospital, Boston, USA, with a gene-edited porcine kidney; eGenesis incorporating the deletion of major glycan xenoantigens (sugar molecules on animal cells that cause the human immune system to reject transplanted animal organs), inactivation of porcine endogenous retroviruses (viral genetic sequences integrated directly into the DNA of all pigs that pose a potential safety risk during animal-to-human organ transplants), and insertion of seven human transgenes (human genetic material). The recipient was also put on immunosuppressants to minimise chances of organ rejection. The authors emphasised that this case showed that porcine kidney xenotransplantation can provide prolonged renal support and be discontinued without clinically significant allosensitisation or zoonotic infection. Early cellular rejection resolved with treatment, whereas later graft failure was associated with microvascular injury that progressed to thrombotic microangiopathy despite a negative donor-specific crossmatch, suggesting that mechanisms beyond conventional antibody-mediated rejection contributed to late graft injury.
In this new case study, the patient had kidney failure caused by type 2 diabetes. He had an estimated 9% chance of receiving a human kidney within five years, against a more than 40% risk of dying or being removed from the waiting list.
The report, titled “Porcine kidney xenotransplantation as a bridge to allotransplantation: a first-in-human study,” detailed the procedure performed at Massachusetts General Hospital in Boston. Kidney xenotransplantation offers a potential solution to the organ shortage, but questions remain regarding durability, zoonotic infection risk, and whether the immunological response to the xenograft elicits sensitisation that could complicate subsequent allotransplantation, according to the authors.
Last year’s study titled ‘Xenotransplantation of a Porcine Kidney for End-Stage Kidney Disease’ highlights the first case and how xenotransplantation offers a potential solution to the organ shortage crisis.
