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肺移植术后血栓性微血管病:一项回顾性观察性多中心队列研究。

Thrombotic Microangiopathy After Lung Transplantation: A Retrospective Observational Multicenter Cohort Study.

作者信息

Gazengel Pierre, Bunel Vincent, El-Husseini Kinan, Zaidan Mohamad, Lefevre Edouard, Kessler Romain, Demant Xavier, Falque Loïc, Eschapasse Emmanuel, Villeneuve Thomas, Dauriat Gaelle, Pradère Pauline, Mercier Olaf, Fadel Elie, Picard Clément, Le Pavec Jérôme

机构信息

Pulmonology and Lung Transplantation Department, Marie-Lannelongue Hospital, Groupe Hospitalier Paris-Saint-Joseph, Le Plessis-Robinson, France.

Paris-Sud University, School of Medicine, Paris-Saclay University, Le Kremlin Bicêtre, France.

出版信息

JHLT Open. 2025 Jul 8;9:100335. doi: 10.1016/j.jhlto.2025.100335. eCollection 2025 Aug.

Abstract

BACKGROUND

Thrombotic microangiopathy (TMA) is a well-recognized complication of solid-organ transplantation that chiefly affects the kidneys. The objective of this study was to describe TMA features and outcomes after lung transplantation.

PATIENTS AND METHODS

This retrospective observational study included patients with TMA following lung or heart-lung transplantation at eight French centers in 2006-2023. Univariate and multivariate analyses were done to identify factors associated with outcomes.

RESULTS

Of the 4565 patients, 82 (1.8%) experienced TMA, at a median of 19 [6-34] months after transplantation; among them, 79 were included (51% female; median age 50 [33-61] years). Mortality during the median follow-up of 31 [11-66] months was 38/79 (48%). Etiological factors were above-target calcineurin inhibitor (CNI) trough levels (48%), combined CNI and mTOR inhibitor therapy (23%), and infection (9%). CNI was continued in 70 patients and replaced by belatacept in 9 patients. In the belatacept group, renal function at one year was better but death, bacterial pneumonia, and CMV viremia were more common; none of the differences was significant, perhaps given the small sample size.

CONCLUSION

Mortality was high after TMA in lung or heart-lung transplant recipients. CNI monitoring protocols should be improved to minimize the risk of toxicity. Belatacept instead of CNI therapy was associated with better kidney function but also with higher frequencies of adverse events, suggesting a need for great caution. Studies adequately powered to assess the risk/benefit ratio of belatacept therapy according to the dosing regimen, patient features, and concomitant immunosuppressants are needed.

摘要

背景

血栓性微血管病(TMA)是实体器官移植中一种公认的并发症,主要影响肾脏。本研究的目的是描述肺移植后TMA的特征和结局。

患者与方法

这项回顾性观察性研究纳入了2006年至2023年在法国8个中心接受肺或心肺移植后发生TMA的患者。进行单因素和多因素分析以确定与结局相关的因素。

结果

在4565例患者中,82例(1.8%)发生了TMA,移植后中位时间为19[6 - 34]个月;其中79例被纳入研究(女性占51%;中位年龄50[33 - 61]岁)。在中位随访31[11 - 66]个月期间,死亡率为38/79(48%)。病因包括钙调神经磷酸酶抑制剂(CNI)谷浓度高于目标值(48%)、联合使用CNI和mTOR抑制剂治疗(23%)以及感染(9%)。70例患者继续使用CNI,9例患者改用贝拉西普。在贝拉西普组,1年时的肾功能较好,但死亡、细菌性肺炎和巨细胞病毒血症更常见;鉴于样本量小,这些差异均无统计学意义。

结论

肺或心肺移植受者发生TMA后的死亡率很高。应改进CNI监测方案以将毒性风险降至最低。用贝拉西普替代CNI治疗与更好的肾功能相关,但也与更高的不良事件发生率相关,这表明需要极其谨慎。需要有足够样本量的研究来根据给药方案、患者特征和伴随的免疫抑制剂评估贝拉西普治疗的风险/效益比。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a353/12305175/e7a98a6f3373/gr1.jpg

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