USE OF DE-NOVO mTOR INHIBITORS IN HYPERSENSITZED KIDNEY TRASPLANT RECIPIENTS: EXPERIENCE FROM CLINICAL PRACTICE.

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients, due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with Calcineurin Inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline cPRA ≥ 50% that underwent kidney transplantation from June 2013 to December 2016 in our Unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively Mycophenolic Acid (MPA, n=38) or mTORi (either everolimus or sirolimus, n=33, target trough levels 3-8 ng/ml). RESULTS: Demographic and immunological risk profiles were similar and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection [Hazard Ratio (HR)(Confidence Interval) 0.32 (0.11-0.90), P=0.031 at univariable analysis, and 0.34 (0.11-0.95), P=0.040 at multivariable analysis]. There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de-novo DSAs. Tacrolimus trough levels along the first year were not different between groups (12-month levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/ml for MPA and mTORi group respectively, P=0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.