Immune Checkpoint Inhibitors in Recipients of Renal Allografts

Abstract

Kidney transplant recipients are at increased risk of malignancy as a result of immunosuppression and are increasingly exposed to checkpoint inhibitors (CPIs). However, CPI therapy can precipitate allograft rejection. This review aims to summarize the current literature describing the epidemiology, immunological mechanisms, diagnosis, and treatment of CPI-associated allograft rejection.Initial studies of CPIs suggested allograft rejection post commencement of CPIs occured commonly (40-60%), occurring between 2 and 6 weeks after CPI initiation, with a cancer response rate approaching 50%. More recent studies with predefined, structured immunosuppressive regimens have seen rejection rates of 0-12.5%, with rejection occurring later. Allograft biopsy remains the mainstay of diagnosis; however, noninvasive tools are emerging, including donor-derived cell-free DNA, urinary chemokine assessment, and defining alloreactive T-cell clones prior to or during CPI therapy.

Keywords: Checkpoint inhibitors; kidney transplant; malignancy; rejection.