A CNI-sparing protocol in lung transplantation

Lung transplantation is an established therapy for end-stage lung diseases, however, long-term outcomes are severely affected by comorbidities and development of chronic rejection. Among all comorbidities kidney insufficiency is the one of the most frequent (5-years rate 54%, 10-years rate 71%) and it is mainly caused by the cumulative effect of calcineurin-inhibitors (CNIs). During the last years, significant efforts have been made to improve kidney function and different immunosuppression strategies have been developed with this purpose. Currently, the most used protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression. Our center has pioneered the use of alemtuzumab as induction therapy. This agent has the potential to reduce drastically recipients` immune cells directed against the new organ. The use of alemtuzumab followed by a low dose double-drug maintenance immunosuppression led to better kidney function along with excellent results in terms of rejection and survival. This trial proposes a new protocol based on alemtuzumab induction and the combined use of two immunosuppressive agents (tacrolimus and everolimus) in a reduced dosis. The addition of everolimus may have a two-fold advantage: 1) further reduction of tacrolimus, which damages the kidney and 2) stimulation of a particular set of recipients` cells responsible for the acceptance of the new organ. One-hundred ten patients will be randomized in two groups. Treatment group will receive the new proposed protocol based on low dose tacrolimus and low dose everolimus and the control group will receive our standard immunosuppression protocol. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of recruitment. In parallel, the composition of the immune cells of the patients will be assessed to understand the impact of the two protocols. The newly proposed immunosuppression strategy may have a direct impact on recipients` life. In fact it could reduce the incidence of drug-related comorbidities and the incidence of rejection, improving as a consequence survival and quality of life.