Recent progress in xenotransplantation and its application to pediatric kidney disease.

Abstract

Patients with kidney failure require dialysis or kidney transplantation. Kidney transplantation offers great benefits, including reduced mortality; however, many patients who wish to undergo kidney transplantation are unable to do so due to a shortage of donor organs. This shortage is a global issue, and xenotransplantation has emerged as a potential solution. The history of xenotransplantation is characterized by overcoming the immunological challenge of hyperacute rejection. Recently, breakthroughs such as gene-edited pigs and novel immunosuppressants have successfully lowered rejection rates. Recent clinical studies have reported transplants in patients diagnosed with brain death, and in March 2024, a gene-edited pig kidney was transplanted into a patient with kidney failure at Massachusetts General Hospital, marking the first instance of a gene-edited xenotransplantation into a living patient. Our research focuses on applying xenotransplantation in pediatric and obstetric fields, specifically exploring fetal therapy using pig fetal kidneys. We have long been researching the development of a novel kidney replacement therapy involving the transplantation of fetal pig kidneys. Fetal pig kidneys have the advantage of not requiring vascular anastomosis and are less likely to be rejected compared to adult pig kidneys. Currently, we are advancing nonhuman primate studies aimed at clinical trials of pig fetal kidney transplant therapy for fetuses diagnosed with Potter syndrome, characterized by bilateral kidney agenesis. We sincerely hope that xenotransplantation will soon become a viable treatment option for adult, pediatric, and fetal patients with kidney failure.