Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience
Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience
复制标题
DOI：
10.1186/s40425-018-0478-8
复制
发表时间：
2019-01-06
影响因子：
10.9
通讯作者：
Abudayyeh, Ala
中科院分区：
文献类型：
--
作者：
Mamlouk, Omar;Selamet, Umut;Abudayyeh, Ala
基本原理和目的免疫检查点抑制剂（CPI）已批准的治疗适应症正在迅速扩大，包括辅助治疗，与 CPI 相关的免疫相关毒性可能会限制这些药物的疗效。关于 CPI 肾毒性的文献有限。在这里，我们介绍了活检证实由 CPI 诱发的急性肾小管间质性肾炎 (ATIN) 和肾小球肾炎 (GN) 的病例，并讨论了这些不良反应的潜在机制。研究设计、设置和参与者我们回顾性回顾了 2008 年至 2018 年接受 CPI 治疗并随后在德克萨斯大学 MD 安德森癌症中心接受肾活检的所有癌症患者。结果我们确定了 16 例诊断为晚期实体或血液学疾病的病例恶性肿瘤； 12 名患者为男性，中位年龄为 64 岁（范围 38 至 77 岁）。从开始 CPI 到发生急性肾损伤 (AKI) 的中位时间为 14 周（范围 6-56 周）。从 AKI 诊断到获得肾活检的平均时间为 16 天（范围从 1 到 46 天）。 15 例发生在抗 PD-1 治疗后。 ATIN 是活检中最常见的病理发现（16 例中的 14 例），几乎所有病例都表现为主要的镜下发现或与其他肾小球病变（少免疫性肾小球肾炎、膜性肾小球肾炎、C3 肾小球肾炎、免疫球蛋白 A (IgA) 肾病或淀粉样蛋白 A (AA) 淀粉样变性）相关的轻度间质性炎症。 16 例中有 15 例停止了 CPI。大多数病例使用类固醇和进一步的免疫抑制来治疗 ATIN 和肾小球肾炎（16 例中的 14 例），其中大多数实现肾功能完全或部分恢复。结论我们的数据表明，CPI 相关的 AKI 在 CPI 治疗后相对较晚发生。我们的活检数据表明 ATIN 是最常见的病理发现；然而，它经常与其他肾小球病变同时发生，这可能需要皮质类固醇以外的免疫抑制治疗。在缺乏预测性血液或尿液生物标志物的情况下，我们建议对 CPI 相关 AKI 进行肾活检。
Rationale & ObjectiveThe approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects.Study design, setting, & participantsWe retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center.ResultsWe identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14weeks (range 6-56weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16days (range from 1 to 46days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery.ConclusionsOur data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.