Thirty-day ciprofloxacin prophylaxis in kidney transplant recipients is associated with a lower rate of BKV infection at 3 months but not at 12 months. The long-term effectiveness and optimal duration of fluoroquinolone prophylaxis against BKV infection remain unknown.

Recent findings suggest that a chronic alloimmune response is playing the dominant role in late allograft loss, challenging the notion that most grafts are lost due to the inexorable progression of calcineurin inhibitor (CNI) nephrotoxicity. CNIs have failed to improve long-term outcomes and are associated with multiple metabolic derangements. Thus, improvement in long-term allograft outcomes may depend on new agents with novel mechanisms of action, devoid of the toxicities associated with CNIs. To meet this need, inhibitors of novel pathways in B cell and plasma cell activation have emerged to combat the humoral immune response including belimumab and atacicept, both promising targets of B-cell survival factors and bortezomib and eculizumab, agents currently in trials for desensitization protocols and treatment of antibody-mediated rejection. Promising agents for maintenance immunosuppression, used as monotherapy or synergistically, include monoclonal antibodies and fusion receptor proteins targeting the CD40-CD154 pathway (multiple anti-CD40 antibodies), the CD28-CD80/86 pathway (i.e., belatacept), the LFA3-CD2 pathway (i.e., alefacept), and small molecules such as tofacitinib, a janus kinase 1/3 inhibitor. The induction of allograft tolerance has been attempted with some success with simultaneous bone marrow/kidney transplantation from the same donor, albeit, limited by its associated toxicites. Finally, the exciting fields of tissue engineering and stem cell biology with the repopulation of decellularized organs is ushering in a new paradigm for transplantation. The era of simplified immunosuppression regimens devoid of toxicities is upon us with the promise of dramatic improvement in long term survival.

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Background. It is estimated that 19.2% of kidneys exported for candidates with >98% calculated panel reactive antibodies are transplanted into unintended recipients, most commonly due to positive physical crossmatch (PXM). We describe the application of a virtual crossmatch (VXM) that has resulted in a very low rate of transplantation into unintended recipients. Methods. We performed a retrospective review of kidneys imported to our center to assess the reasons driving late reallocation based on the type of pretransplant crossmatch used for the intended recipient. Results. From December 2014 to October 2017, 254 kidneys were imported based on our assessment of a VXM. Of these, 215 (84.6%) were transplanted without a pretransplant PXM. The remaining 39 (15.4%) recipients required a PXM on admission using a new sample because they did not have an HLA antibody test within the preceding 3 months or because they had a recent blood transfusion. A total of 93% of the imported kidneys were transplanted into intended recipients. There were 18 late reallocations: 9 (3.5%) due to identification of a new recipient medical problem upon admission, 5 (2%) due to suboptimal organ quality on arrival, and only 4 (1.6%) due to a positive PXM or HLA antibody concern. A total of 42% of the recipients of imported kidneys had a 100% calculated panel reactive antibodies. There were no hyperacute rejections and very infrequent acute rejection in the first year suggesting no evidence for immunologic memory response. Conclusions. Seamless sharing is within reach, even when kidneys are shipped long distances for highly sensitized recipients. Late reallocations can be almost entirely avoided with a strategy that relies heavily on VXM.

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