Preventing kidney graft dysfunction and rejection is a critical step in addressing the nationwide organ shortage and improving patient outcomes. While kidney transplants (KT) are performed more frequently, the overall number of patients on the waitlist consistently exceeds organ availability. Despite improved short-term outcomes in KT, comparable progress in long-term allograft survival has not been achieved. Major cause of graft loss at 5 years post-KT is chronic allograft dysfunction (CAD) characterized by interstitial fibrosis and tubular atrophy (IFTA). Accordingly, proactive prevention of CAD requires a comprehensive understanding of the immune mechanisms associated with either further dysfunction or impaired repair. Allograft rejection is primed by innate immune cells and carried out by adaptive immune cells. The rejection process is primarily facilitated by antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR). It is essential to better elucidate the actions of individual immune cell subclasses (e.g. B memory, Tregs, Macrophage type 1 and 2) throughout the rejection process, rather than limiting our understanding to broad classes of immune cells. Embracing multi-omic approaches may be the solution in acknowledging these intricacies and decoding these enigmatic pathways. A transition alongside advancing technology will better allow organ biology to find its place in this era of precision and personalized medicine.
Keywords: Acute rejection; Alloimmune response; Chronic allograft dysfunction; Immune cells; Kidney transplantation; Single cell approaches.
© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.