依库珠单抗作为肺移植后血栓性微血管病的挽救性治疗。

Eculizumab as Salvage Treatment for Thrombotic Microangiopathy After Lung Transplantation.

机构信息

Nephrology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

Nephrology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.

出版信息

Clin Transplant. 2024 Sep;38(9):e15443. doi: 10.1111/ctr.15443.

DOI:10.1111/ctr.15443

PMID:39207183

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 × 10/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.

摘要

背景

血栓性微血管病（TMA）是肺移植（LT）后的一种罕见并发症，很少有详细描述。最近的证据表明，除原发性非典型溶血尿毒症综合征（aHUS）外，TMA 与补体替代途径的过度激活有关。本研究的重点是分析 LT 后 TMA 中依库珠单抗的治疗反应。

方法

我们研究了来自西班牙 2 个三级医疗中心的 11 例 LT 后 TMA 患者的病例系列。提供了临床数据和依库珠单抗的反应率。

结果

LT 的主要适应证是慢性阻塞性肺疾病（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），大多数情况下（73%）的 TMA 触发因素是免疫抑制剂。血小板和血红蛋白最低值分别为 58×10/µL（24-108）和 7.7g/dL（7.1-7.9）。所有病例均出现急性肾损伤（AKI），肌酐中位数为 4mg/dL（3.2-4.8），54.5%需要急性透析。依库珠单抗开始使用的中位时间为 8 天（6-14），中位持续时间为 3 周（2-8）。7 例（63.6%）观察到完全 TMA 反应，10 例（90.9%）观察到血液学反应。血液学和肾脏反应的时间分别为 23 天（13-29）和 28 天（14-46）。