Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study
Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study
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免疫检查点抑制剂相关阿基的临床特征和结局：一项多中心研究
DOI：
10.1681/asn.2019070676
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发表时间：
2020-02-01
影响因子：
13.6
通讯作者：
Leaf, David E.
中科院分区：
文献类型：
--
作者：
Cortazar, Frank B.;Kibbelaar, Zoe A.;Leaf, David E.
尽管人们越来越认识到免疫检查点抑制剂相关AKI的重要性，但关于这种免疫治疗并发症的数据很少。方法：我们对138例免疫检查点抑制剂相关AKI患者进行了一项多中心研究，定义为血清肌酐升高2倍或直接归因于免疫检查点抑制剂的新透析需求。我们还收集了276名接受这些药物治疗但未发生AKI的对照患者的数据。结果较低的基线eGFR、质子泵抑制剂的使用和联合免疫检查点抑制剂治疗均与免疫检查点抑制剂相关的AKI风险增加独立相关。从免疫检查点抑制剂开始到AKI的中位时间（四分位数范围）为14（6-37）周。大多数患者有亚肾病性蛋白尿，约一半有脓尿。43%的患者发生肾外免疫相关不良事件;69%的患者同时接受可能引起肾小管间质性肾炎的药物治疗。60例活检患者中93%以肾小管间质性肾炎为主。大多数患者（86%）接受类固醇治疗。肾完全恢复、部分恢复和无肾恢复的患者分别为40%、45%和15%。同时发生的肾外免疫相关不良事件与肾脏预后恶化相关，而同时发生的引起小管间质性肾炎的药物和类固醇治疗均与肾脏预后改善相关。免疫检查点抑制剂相关AKI后未能实现肾脏恢复与较高的死亡率独立相关。22%的患者出现免疫检查点抑制剂免疫应答挑战，其中23%的患者发生复发性相关AKI。结论：这项多中心研究确定了免疫检查点抑制剂相关AKI患者的危险因素、临床特征、组织病理学结果、肾脏和总体预后。
Background Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse.Methods We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a > 2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI.Results Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechal lenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI.Conclusions This multicenter study identifies insights into the riskfactors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.