USE OF DE-NOVO mTOR INHIBITORS IN HYPERSENSITZED KIDNEY TRASPLANT RECIPIENTS: EXPERIENCE FROM CLINICAL PRACTICE.
TRANSPLANTATION(2020)
摘要
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 calculated panel reactive antibody (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 [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 donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo 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.
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关键词
hypersensitized kidney transplant recipients,de novo mtor inhibitors,kidney transplant recipients
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