免疫检查点抑制剂相关 AKI 的临床特征和结局：一项多中心研究。
Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.
机构信息
Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts;
New York Nephrology Vasculitis and Glomerular Center, Albany, New York.
出版信息
J Am Soc Nephrol. 2020 Feb;31(2):435-446. doi: 10.1681/ASN.2019070676. Epub 2020 Jan 2.
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 rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI.
CONCLUSIONS
This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
背景
尽管人们越来越认识到免疫检查点抑制剂相关急性肾损伤的重要性，但关于免疫治疗相关 AKI 的数据仍然很少。
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，该 AKI 定义为血清肌酐升高≥2 倍或新需要透析，且直接归因于免疫检查点抑制剂。我们还收集了 276 例接受这些药物但未发生 AKI 的对照患者的数据。
结果
基线时估算肾小球滤过率较低、质子泵抑制剂的使用和联合免疫检查点抑制剂治疗与免疫检查点抑制剂相关 AKI 的风险增加独立相关。免疫检查点抑制剂开始至 AKI 的中位（四分位间距）时间为 14（6-37）周。大多数患者有亚肾病范围蛋白尿，约一半有脓尿。43%的患者发生了肾外免疫相关不良事件；69%的患者同时接受了潜在的致间质性肾炎药物治疗。60 例活检患者中，93%的患者存在间质性肾炎。大多数患者（86%）接受了类固醇治疗。分别有 40%、45%和 15%的患者完全、部分或无肾脏恢复。同时发生的肾外免疫相关不良事件与更差的肾脏预后相关，而同时发生的致间质性肾炎药物和类固醇治疗与改善的肾脏预后相关。免疫检查点抑制剂相关 AKI 后未能实现肾脏恢复与更高的死亡率独立相关。22%的患者再次接受免疫检查点抑制剂治疗，其中 23%的患者再次发生 AKI。
结论
这项多中心研究确定了免疫检查点抑制剂相关 AKI 患者的风险因素、临床特征、组织病理学发现以及肾脏和总体结局的见解。
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