Can mouse kidney transplant models inform mechanisms of injury and acceptance in clinical kidney transplantation?

Abstract

Despite standard-of-care immunosuppression, acute rejection remains commonly observed in kidney transplants and leads to chronic graft injury and failure in many transplanted patients. Mechanisms underlying acute and chronic kidney graft injury are incompletely understood, undermining the development and implementation of therapeutic strategies to improve outcomes. This compels the use of preclinical kidney transplant models to identify components and mechanisms mediating acute and chronic graft injury. Mouse models have been instrumental in establishing basic principles of alloimmune responses and the rejection of heart allografts. There is increasing use of mouse models to extend these studies to kidney transplantation, but the relevance of the findings to clinical kidney transplants remains under scrutiny. Here, we discuss the strengths and weaknesses of mouse models of kidney allograft responses and injury. Although obvious weaknesses arise when considering the relevance to clinical kidney transplants, there are new models that recapitulate many features of kidney graft injury in the clinical scenario and have much to contribute to understanding innate and donor alloantigen-specific mechanisms underlying kidney allograft injury. As in most preclinical studies, the pertinent use of kidney allogeneic transplants in mice comes down to the judicious choice of test questions and the choice of appropriate donors and recipients for the chosen model.

Keywords: kidney transplantation; mouse models; rejection; surgical approaches; tolerance.