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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.
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.
摘要：
背景：急性肾损伤（AKI）已被描述为免疫检查点抑制剂治疗的并发症。我们介绍了一系列患者，大多数患有肺腺癌，他们在积极接受免疫检查点抑制剂的同时发展了AKI。
方法：这是一个回顾性分析的临床病例系列，其中6例患者在希望市综合癌症中心接受治疗。收集了性别数据，年龄,种族,合并症,合并用药,恶性肿瘤的类型，治疗,和肾功能。所有患者均接受肾活检以对AKI的机制进行分类。对所有患者的肿瘤组织进行综合基因组分析(CGP)。
结果：AKI的类型包括急性间质性肾炎和急性肾小管坏死。促成因素包括使用已知有助于AKI的伴随药物。除两名患者外，所有患者均使用类固醇完全解决了AKI。在CGP上发现了几个值得注意的突变,包括外显子20插入以及多个NF1和TP53突变。在6例患者中，有2例患者在肿瘤组织上有高PD-L1表达。除了AKI,一部分患者有蛋白尿,活检显示相应的肾小球病变为微小病变和局灶性和节段性肾小球硬化.
结论：我们的病例系列表明，来自免疫检查点抑制剂的AKI具有可变的表现，可能需要个体化治疗方法。需要进一步的研究来确定可能有助于识别有风险的生物标志物并指导这种疾病的管理。
方法：这是一个回顾性分析的临床病例系列，其中6例患者在希望市综合癌症中心接受治疗。收集了性别数据，年龄,种族,合并症,合并用药,恶性肿瘤的类型，治疗,和肾功能。所有患者均接受肾活检以对AKI的机制进行分类。对所有患者的肿瘤组织进行综合基因组分析(CGP)。
结果：AKI的类型包括急性间质性肾炎和急性肾小管坏死。促成因素包括使用已知有助于AKI的伴随药物。除两名患者外，所有患者均使用类固醇完全解决了AKI。在CGP上发现了几个值得注意的突变,包括外显子20插入以及多个NF1和TP53突变。在6例患者中，有2例患者在肿瘤组织上有高PD-L1表达。除了AKI,一部分患者有蛋白尿,活检显示相应的肾小球病变为微小病变和局灶性和节段性肾小球硬化.
结论：我们的病例系列表明，来自免疫检查点抑制剂的AKI具有可变的表现，可能需要个体化治疗方法。需要进一步的研究来确定可能有助于识别有风险的生物标志物并指导这种疾病的管理。
