Eculizumab as Salvage Treatment for Thrombotic Microangiopathy After Lung Transplantation

IF 1.9 4区医学 Q2 SURGERY Clinical Transplantation Pub Date : 2024-08-29 DOI:10.1111/ctr.15443

Hernando Trujillo, Ana Huerta, Rodrigo Alonso, Maria Luisa Serrano, Myriam Aguilar, Enrique Morales, Teresa Cavero

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Abstract

Background

Thrombotic microangiopathy (TMA) is a rare complication after lung transplantation (LT) that has seldom been characterized in detail. Recent evidence has linked TMA other than primary atypical hemolytic uremic syndrome (aHUS) with hyperactivation of the complement alternative pathway. The focus of this investigation was to analyze the treatment response with eculizumab in TMA after LT.

Methods

Case series where we have studied 11 patients with TMA after LT from 2 Spanish tertiary healthcare centers. Clinical data and response rates to eculizumab are provided.

Results

The main indication for lung transplant was chronic obstructive pulmonary disease (COPD) (36%) and most cases (82%) received bilateral LT. The median time to TMA diagnosis was 11.6 months (4.7–28.9) and the TMA trigger in the majority of cases (73%) was immunosuppressive drugs. Platelet and hemoglobin nadir were 58 × 10³/µL (24–108) and 7.7 g/dL (7.1–7.9), respectively. All cases presented acute kidney injury (AKI) with a median creatinine of 4 mg/dL (3.2–4.8) and 54.5% required acute dialysis. Eculizumab was started after a median time of 8 days (6–14) with a median duration of 3 weeks (2–8). Complete TMA response was observed in 7 (63.6%) cases and hematologic response in 10 (90.9%). The time to hematologic and renal response was 23 days (13–29) and 28 days (14–46), respectively.

Conclusions

TMA after LT is infrequent but potentially devastating. Our findings suggest that short cycles of eculizumab may be effective for severe TMA after LT.

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将 Eculizumab 作为肺移植术后血栓性微血管病的挽救疗法

背景血栓性微血管病（TMA）是肺移植（LT）后的一种罕见并发症，很少有详细的描述。最近有证据表明，除原发性非典型溶血性尿毒综合征（aHUS）外，血栓性微血管病还与补体替代途径的过度激活有关。本研究的重点是分析依库珠单抗对 LT 后 TMA 的治疗反应。方法我们对来自西班牙两家三级医疗中心的 11 名 LT 后 TMA 患者进行了病例系列研究。提供了临床数据和对依库珠单抗的反应率。结果肺移植的主要适应症是慢性阻塞性肺病（COPD）（36%），大多数病例（82%）接受了双侧LT。TMA诊断的中位时间为11.6个月（4.7-28.9个月），大多数病例（73%）的TMA诱因是免疫抑制剂。血小板和血红蛋白最低值分别为 58 × 103/µL (24-108) 和 7.7 g/dL (7.1-7.9)。所有病例均出现急性肾损伤（AKI），肌酐中位数为 4 mg/dL (3.2-4.8)，54.5% 的病例需要急性透析。开始使用依库珠单抗的中位时间为 8 天（6-14 天），中位持续时间为 3 周（2-8 周）。7例（63.6%）观察到完全的TMA反应，10例（90.9%）观察到血液学反应。血液学和肾脏反应时间分别为 23 天（13-29 天）和 28 天（14-46 天）。结论 LT 后的 TMA 并不常见，但可能具有破坏性。我们的研究结果表明，短周期的依库珠单抗可能对LT后的严重TMA有效。

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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.