Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections

Abstract

Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.

Guidelines for the assessment and acceptance of potential brain-dead organ donors

“…All blood culture results should be verified and communicated to the transplantation center. ( 126 , 127 )…”

Potential yield of imminent death kidney donation

“…The rationale for each of these criteria is described in Table S1. The second query excluded patients < 18 years old and patients with metastatic cancer, as successful transplants have been reported from individuals with some of the exclusionary criteria used for the first query, including donors over age 60(19, 20), donors with bacteremia and other bloodstream infections (21–23), and HIV-positive to HIV-positive transplants. (24) We estimate that the actual number of potential imminent death kidney donors falls between these two estimates.…”

Diverse Routes of Allograft Tolerance Disruption by Memory T Cells

“…While such efforts are clearly warranted, there are potentially alternative routes whereby T cell memory could impair tolerance induction without a requirement for substantial heterologous immunity to the donor MHC (43). Unfortunately, the metagenome of both organ donors and recipients encode a variety of non-self antigens, such as those derived from microbiota (44,45) or from latent infections such as CMV and EBV (46)(47)(48)(49) that are clearly associated with impaired allograft outcomes in clinical transplantation. It is clear that the activation of anti-viral immunity can abrogate allograft tolerance (50,51), possibly by the induction of inflammation that itself may non-specifically impair tolerance induction (52,53).…”

“…In what situation might this type of memory cell reactivity be important in transplantation? In the setting of autoimmunity or c donor pathogen infections such as CMV and EBV (46)(47)(48)(49), the host could be immune to donor-derived, non-MHC antigens without obvious pre-transplant anti-donor MHC immunity. However, depending on the tissue distribution of autoantigens or donor pathogen-derived antigens, memory cells for these antigens could disrupt tolerance induction by diverting the naïve T cells recognizing the same APC from a tolerized fate to an effector phenotype (Figure 2).…”