Pathophysiology of rejection in kidney transplantation

Rejection remains a major obstacle to successful kidney transplantation. The complex pathophysiology of rejection depends on a fine-tuned interplay between the innate and adaptive immune systems.

This review provides a comprehensive analysis of the pathophysiology of rejection of kidney grafts, performed through careful selection of most relevant papers available on the topic in the PubMed database. The two types of rejection usually observed at the kidney biopsy, i.e. cellular and humoral rejection, are described with an accurate outline of the biological processes that lead to their development.

The incidence of T-cell-mediated rejection is decreasing, and most cases promptly respond to appropriate immunosuppression. However, late diagnosis or incomplete response to treatment may have deleterious consequences in the long term. The main issue is represented by antibody-mediated rejection, which unsatisfactorily responds to aggressive immunosuppression, especially when diagnosed late. Prevention of acute ABMR rests on HLA-specific antibody detection prior to transplantation, adequate immunosuppression, and optimal patients' compliance. Late diagnosis and poor response to treatment inevitably lead to chronic ABMR, for which no therapies are currently available.