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在选定的儿科心脏移植受者中使用无 CNI 免疫抑制的长期经验。

Long-term experience using CNI-free immunosuppression in selected paediatric heart transplant recipients.

机构信息

Department for Congenital Heart Disease/Pediatric Cardiology, German Heart Institute, Berlin, Germany.

Department for Pediatric Cardiology, Charité Universitätsmedizin, Berlin, Germany.

出版信息

Pediatr Transplant. 2021 Dec;25(8):e14111. doi: 10.1111/petr.14111. Epub 2021 Aug 18.

Abstract

BACKGROUND

CNI-free immunosuppression with conversion to mTORi-based immunosuppression has been demonstrated to reduce CNI-toxicity and to exhibit anti-proliferative properties. However, the experience of CNI-free immunosuppression in paediatric heart transplantation is limited.

METHODS

A retrospective analysis was conducted of 129 paediatric heart transplants performed between 1997 and 2015. Fifteen patients with clinically indicated conversion from CNI-based to CNI-free immunosuppression were identified. Survival data, rejection episodes, renal function, post-transplantation lymphoproliferative disorder and CAV, including examination with OCT were analysed.

RESULTS

Immunosuppression conversion was successful in all patients. Fourteen of 15 patients (93%) are currently living with good graft function. Median post-transplant survival was 15 years (range, 5-23 years), and median follow-up since conversion was 6 years (range, 1-11 years). Mild (grade 1R) ACR was present in three patients after discontinuation of CNIs. The recovery of renal function with a significant increase in eGFR was observed at 1 and 3 years after conversion. No patient had angiographic signs of macroscopic CAV according to the current ISHLT classification; however, OCT showed the signs of angiographically silent CAV in all patients. CAV did not progress in any patient, implying CAV was stabilised by mTORi-based CNI-free immunosuppression.

CONCLUSIONS

CNI-free immunosuppression based on mTORis is a safe and appropriate strategy for maintenance therapy in selected paediatric patients, significantly improves renal function and stabilises CAV. OCT revealed early development of angiographically silent CAV.

摘要

背景

无钙调磷酸酶抑制剂(CNI)免疫抑制方案转换为以 mTOR 抑制剂为基础的免疫抑制方案,已被证实可降低 CNI 的毒性,并具有抗增殖作用。然而,无 CNI 免疫抑制方案在儿科心脏移植中的应用经验有限。

方法

回顾性分析了 1997 年至 2015 年期间进行的 129 例儿科心脏移植。确定了 15 例临床需要从 CNI 为基础的免疫抑制方案转换为无 CNI 免疫抑制方案的患者。分析了生存数据、排斥反应、肾功能、移植后淋巴增生性疾病和 CAV,包括 OCT 检查。

结果

所有患者的免疫抑制转换均成功。15 例患者中有 14 例(93%)目前移植心脏功能良好。中位移植后生存时间为 15 年(范围为 5-23 年),转换后中位随访时间为 6 年(范围为 1-11 年)。3 例患者在停用 CNI 后出现轻度(1R 级)急性细胞性排斥反应。转换后 1 年和 3 年时观察到肾功能恢复,eGFR 显著增加。根据目前的 ISHLT 分类,没有患者出现宏观 CAV 的血管造影迹象;然而,OCT 显示所有患者均存在血管造影隐匿性 CAV 的迹象。没有患者的 CAV 进展,这意味着 mTOR 抑制剂为基础的无 CNI 免疫抑制方案稳定了 CAV。

结论

基于 mTOR 抑制剂的无 CNI 免疫抑制方案是一种安全且适当的选择,可用于维持治疗选定的儿科患者,显著改善肾功能并稳定 CAV。OCT 显示了早期发生的血管造影隐匿性 CAV。

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