Ramya Muddasani, Neel Talwar, Isa Mambetsariev, Jeremy Fricke, Mercury Lin, Daniel Schmolze, Andrew Yue, Amna Rizvi, Ravi Salgia
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引用次数: 0
Abstract
Background: Acute kidney injury (AKI) has been well described as a complication of immune checkpoint inhibitor therapy. We present a series of patients, the majority with lung adenocarcinoma, who developed AKI while actively receiving immune checkpoint inhibitors.
Methods: This is a retrospectively analyzed clinical case series of six patients treated at City of Hope Comprehensive Cancer Center. Data were collected on gender, age, ethnicity, comorbidities, concomitant medications, type of malignancy, treatments, and renal function. All patients underwent renal biopsy for classification of the mechanism of AKI. Comprehensive genomic profiling (CGP) was performed on tumor tissue for all patients.
Results: Patterns of AKI included acute interstitial nephritis and acute tubular necrosis. Contributing factors included the use of concomitant medications known to contribute to AKI. All but two patients had full resolution of the AKI with the use of steroids. There were several mutations found on CGP that was notable including an Exon 20 insertion as well as multiple NF1 and TP53 mutations. There was high PD-L1 expression on tumor tissue noted in two out of six patients. In addition to AKI, a subset of patients had proteinuria with biopsies revealing corresponding glomerular lesions of minimal change disease and focal and segmental glomerulosclerosis.
Conclusions: Our case series demonstrates that AKI from immune checkpoint inhibitors has a variable presentation that may require an individualized treatment approach. Further studies are needed to identify biomarkers that may help identify those at risk and guide the management of this condition.
背景:急性肾损伤(AKI)作为免疫检查点抑制剂治疗的一种并发症已被广泛描述。我们介绍了一系列在积极接受免疫检查点抑制剂治疗期间出现急性肾损伤的患者,其中大部分患者为肺腺癌患者:这是一个回顾性分析的临床病例系列,涉及在希望之城综合癌症中心接受治疗的六名患者。收集的数据包括性别、年龄、种族、合并症、伴随药物、恶性肿瘤类型、治疗方法和肾功能。所有患者都接受了肾活检,以便对 AKI 的机制进行分类。对所有患者的肿瘤组织进行了全面基因组分析(CGP):结果:AKI的模式包括急性间质性肾炎和急性肾小管坏死。诱发因素包括同时使用已知会导致 AKI 的药物。除两名患者外,所有患者在使用类固醇后都完全缓解了AKI。CGP上发现了几个值得注意的突变,包括一个外显子20插入以及多个NF1和TP53突变。六名患者中有两名患者的肿瘤组织中出现了 PD-L1 高表达。除了 AKI 外,部分患者还出现蛋白尿,活检显示相应的肾小球病变,包括微小病变、局灶性和节段性肾小球硬化:我们的系列病例表明,免疫检查点抑制剂引起的 AKI 表现各异,可能需要个体化的治疗方法。还需要进一步研究来确定生物标志物,以帮助识别高危人群并指导该病症的治疗。
期刊介绍:
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.