Differences between xenotransplantation and allogeneic kidney transplantation: the current situation and future challenges in Japan

Kidney transplantation is the only curative option for patients with chronic renal failure, significantly improving their survival and quality of life. However, this treatment remains limited by the shortage of organ donors. The shortage of kidney donors remains a serious problem all over the world, and is particularly severe in Japan. While advancements in immunosuppressive therapies and histocompatibility testing have improved outcomes in allogeneic kidney transplantation, the rising number of dialysis patients has worsened the gap between the demand for and supply of suitable donor organs. In response to this pressing need, xenotransplantation has gained attention as a promising alternative solution. Recent progress driven by gene-editing technologies, including CRISPR-Cas9, has facilitated the development of genetically modified pigs suitable for potential human transplantation. This review provides an overview of the key differences in immune response and infection risks between xenogeneic and allogeneic kidney transplants. In addition, it comprehensively examines the challenges and potential of xenogeneic kidney transplantation from multiple perspectives, including differences in immunosuppressive therapies between allogeneic and xenogeneic transplantation. We also discuss the feasibility of xenogeneic kidney transplantation as a solution to the organ shortage in Japan and present directions for addressing challenges toward clinical application. We hope this review will provide valuable insights into the potential of xenogeneic kidney transplantation as a new treatment option for chronic renal failure and contribute to efforts to address the donor shortage problem in Japan.