Rapamycin in transplantation: A review of the evidence. The calcineurin inhibitors have been the mainstays of immunosuppression for solid organ transplantation over the last two decades, but nephrotoxicity limits their therapeutic benefit. Rapamycin is a new drug with both immunosuppressant and antiproliferative properties that has a unique mechanism of action distinct from that of the calcineurin inhibitors. It has a role as a maintenance immunosuppressant either alone or in combination with a calcineurin inhibitor and can also be used to treat refractory acute rejection. Theoretical evidence suggests that it may limit the development and progression of chronic rejection in transplant recipients, but this has yet to be confirmed. This review examines the current in vitro animal and human work underlying the use of rapamycin and, in addition, comments on the pharmacokinetics and side-effect profile of this promising new agent.

Ex vivo normothermic perfusion (EVNP) is a novel method of preservation that restores circulation and allows an organ to regain function prior to transplantation. The aim of this study was to assess the effects of EVNP in kidneys from marginal donors. Eighteen kidneys from extended criteria donors (ECD) underwent a period of EVNP immediately before transplantation. Kidneys were perfused with a plasma free redcell based solution at a mean temperature of 34.6• C. The outcome of these kidneys was compared to a control group of 47 ECD kidneys that underwent static cold storage (CS). The mean donor age was 61 ± 1 years in the EVNP and 62 ± 6 years in the CS group (p = 0.520). EVNP kidneys were perfused for an average of 63 ± 16 min and all were transplanted successfully. The delayed graft function rate (DGF), defined as the requirement for dialysis within the first 7 days was 1/18 patients (5.6%) in the EVNP group versus 17/47 (36.2%) in the CS group (p = 0.014). There was no difference in graft or patient survival at 12 months (p = 0.510, 1.000). This first series of EVNP in renal transplantation demonstrates that this technique is both feasible and safe. Our preliminary data suggests that EVNP offers promise as a new technique of kidney preservation.

The incidence of clinically significant complications after protocol biopsy of a stable renal transplant is low. Direct benefits to the patients concerned (irrespective of the benefit that may accrue in clinical trials) were not formally assessed but seem likely to outweigh the risk of the procedure. We believe that it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care.

We conclude that ex vivo normothermic kidney perfusion with a plasma-free red cell-based solution is a feasible method of preservation. This first case was performed without compromising the transplant kidney.