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免疫检查点抑制剂所致急性间质性肾炎的诊断、管理及结局:单中心经验

Diagnosis, management, and outcomes of immune checkpoint inhibitor induced acute interstitial nephritis: A single-center experience.

作者信息

Elghawy Omar, Patel Reema, Barsouk Adam, Puthumana Joe, Xu Jason, Sussman Jonathan, Horton Bethany, Kaur Varinder

机构信息

Department of General Internal Medicine, University of Pennsylvania, Philadelphia, PA, USA.

University of Virginia Cancer Center, Charlottesville, VA, USA.

出版信息

J Oncol Pharm Pract. 2025 Jun;31(4):641-648. doi: 10.1177/10781552241252627. Epub 2024 May 5.

Abstract

BackgroundImmune checkpoint inhibitor (ICI)-associated acute interstitial nephritis (AIN) is a recognized complication of immunotherapy (IO), but literature on its management and outcomes is limited.MethodsWe retrospectively reviewed patients who received ICIs and developed biopsy-proven or clinically-suspected ICI-associated AIN at the University of Virginia Comprehensive Cancer Center from 2012-2023. We analyzed baseline characteristics and clinical outcomes, including treatment interruption and rechallenge rates. Acute kidney injury (AKI) was defined as a ≥ 1.5-fold increase in baseline creatinine under seven days, a two-fold increase above the upper limit of normal, or an increase by ≥0.3 mg/dL. Kidney function returning to within 0.3 mg/dL or less than twice baseline was considered complete (CRc) and partial (PRc) recovery, respectively.ResultsWe identified 12 cases of ICI-AIN: four by biopsy (33%) and eight (67%) by clinical suspicion. Two patients received anti-CTLA-4 and anti-PD1, six received anti-PD1 alone, and four received chemo-immunotherapy. The majority (58%) of patients developed AIN within the first 5 cycles. Eight patients developed ≥ Grade 3 AKI, and six developed multiple irAEs. ICI was permanently discontinued in seven patients (58%) and temporarily interrupted in four (30%). The CRc and PRc rates were 67% and 8%, respectively. Upon AIN onset, the best disease response was stable disease in five patients, partial response in three, and progressive disease in three. Median overall survival was 4.87 years, and progression-free survival was 1.5 years.ConclusionsRechallenge with IO after kidney irAE may be possible in some patients but requires careful evaluation on an individual basis.

摘要

背景

免疫检查点抑制剂(ICI)相关的急性间质性肾炎(AIN)是免疫治疗(IO)公认的并发症,但关于其管理和结局的文献有限。

方法

我们回顾性分析了2012年至2023年在弗吉尼亚大学综合癌症中心接受ICI治疗并经活检证实或临床怀疑为ICI相关AIN的患者。我们分析了基线特征和临床结局,包括治疗中断和再次治疗率。急性肾损伤(AKI)定义为在7天内基线肌酐水平升高≥1.5倍、高于正常上限两倍或升高≥0.3mg/dL。肾功能恢复到比基线水平高0.3mg/dL以内或低于基线水平两倍分别被视为完全(CRc)和部分(PRc)恢复。

结果

我们确定了12例ICI-AIN患者:4例经活检确诊(33%),8例(67%)经临床怀疑确诊。2例患者接受抗CTLA-4和抗PD1治疗,6例仅接受抗PD1治疗,4例接受化疗免疫治疗。大多数(58%)患者在最初5个周期内发生AIN。8例患者发生≥3级AKI,6例发生多种免疫相关不良反应(irAE)。7例患者(58%)永久停用ICI,4例(30%)暂时中断使用。CRc和PRc率分别为67%和8%。在AIN发病时,最佳疾病反应为5例患者病情稳定,3例部分缓解,3例疾病进展。中位总生存期为4.87年,无进展生存期为1.5年。

结论

在肾脏发生免疫相关不良反应后,部分患者可能可以再次接受IO治疗,但需要对个体进行仔细评估。

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