哺乳动物肺移植后用雷帕霉素（mTOR）抑制剂靶替代钙调磷酸酶抑制剂

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2025-06-14 DOI:10.1111/ctr.70211

Kavya Kommaraju, Muath Alsharif, John P. Scott, Kelly M. Pennington

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引用次数: 0

摘要

钙调磷酸酶抑制剂（CNIs）是肺移植免疫抑制的基础，但与肾毒性和其他不良反应有关。虽然减少剂量和联合西罗莫司（雷帕霉素抑制剂（mTORi）的哺乳动物靶点）已经进行了探索，但完全转化为西罗莫司仍然不常见。本研究描述了肺移植受者完全停用CNI并改用西罗莫司的特点和结果。方法：本回顾性病例系列包括2010年至2021年间转入西罗莫司免疫抑制的52例肺移植受者。统计数据、移植特征、免疫抑制和结果从电子病历中收集。结果男性31例（59.6%），中位年龄58.4岁（IQR 52.3-63.5）。CNI停药的主要指征是肾功能不全（73.1%）。西罗莫司停药的发生率为69.2%，最常见的原因是水肿（25.0%）、肺毒性（19.4%）、排斥反应（19.4%）和手术需要（22.2%）。13.5%的患者出现临床显著排斥反应，其中4例进展为慢性同种异体肺移植功能障碍（chronic lung allograft dysfunction， CLAD）， 2例死亡。16例患者（30.8%）耐受CNI停药超过一年。结论从CNI完全转换为西罗莫司，由于副作用，耐受性差，排斥反应发生率高。需要进一步的研究来优化患者选择和风险缓解策略。

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Calcineurin Inhibitor Replacement With Mammalian Target of Rapamycin (mTOR) Inhibitor Following Lung Transplantation

Introduction

Calcineurin inhibitors (CNIs) are the cornerstone of lung transplant immunosuppression but are associated with nephrotoxicity and other adverse effects. Although dose reduction and combination with Sirolimus, a mammalian target of rapamycin inhibitor (mTORi), have been explored, full conversion to Sirolimus remains uncommon. This study describes the characteristics and outcomes of lung transplant recipients who underwent complete CNI withdrawal and conversion to Sirolimus.

Methods

This retrospective case series included 52 lung transplant recipients transitioned to Sirolimus-based immunosuppression between 2010 and 2021. Data on demographics, transplant characteristics, immunosuppression, and outcomes were collected from electronic medical records.

Results

The cohort included 31 males (59.6%) with a median age of 58.4 years (IQR 52.3–63.5). The primary indication for CNI withdrawal was renal dysfunction (73.1%). Sirolimus discontinuation occurred in 69.2%, most commonly due to edema (25.0%), lung toxicity (19.4%), rejection (19.4%), and surgical needs (22.2%). Clinically significant rejection occurred in 13.5%, with four patients progressing to chronic lung allograft dysfunction (CLAD) and two deaths. Sixteen patients (30.8%) tolerated CNI withdrawal for over a year.

Conclusion

Full conversion from CNI to Sirolimus is poorly tolerated due to side effects and has a high incidence of rejection. Further studies are needed to optimize patient selection and risk mitigation strategies.

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.