Pretransplant Kidney-Specific Treatment to Eliminate the Need for Systemic Immunosuppression

Abstract

Background. Despite significant side effects, chronic systemic immunosuppression remains the backbone of clinical transplantation. We investigated the feasibility of preventing early allorecognition in canine renal allografts using a nonsystemic pretreatment. Methods. The renal vasculature was treated with a bioengineered interface consisting of a nano-barrier membrane during 3 hr of ex vivo warm perfusion. Results. Preliminary feasibility of the immunocloaking technology was established by the following criteria: it is possible to achieve approximately 90% coverage of the vasculature with nano-barrier membrane after 3 hr of ex vivo warm perfusion; covering the luminal surfaces prevents allorecognition as determined by mixed lymphocyte-vascular endothelial reaction; covering the luminal surfaces does not negatively affect renal function as determined by autotransplant outcomes; and graft rejection is significantly postponed in canine kidneys treated with the immunocloaking technology. In the absence of systemic immunosuppression, untreated control dogs experienced a mean onset of rejection on day 6, whereas in the treated dogs with modified renal vascular luminal surfaces, the mean onset of rejection was significantly delayed until day 30. Conclusions. The ability to postpone, or eventually eliminate, the allorecognition that occurs immediately on reperfusion could provide a new window of opportunity to introduce adjunct therapies to support tolerance induction. To our knowledge, this is the first time significantly prolonged canine renal allograft survival has been achieved in the absence of systemic immunosuppression or immunologic manipulation of the recipient.