Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.
Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.
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DOI：
10.1016/j.kint.2016.04.008
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发表时间：
2016-09
影响因子：
19.6
通讯作者：
Leaf DE
中科院分区：
文献类型：
--
作者：
Cortazar FB;Marrone KA;Troxell ML;Ralto KM;Hoenig MP;Brahmer JR;Le DT;Lipson EJ;Glezerman IG;Wolchok J;Cornell LD;Feldman P;Stokes MB;Zapata SA;Hodi FS;Ott PA;Yamashita M;Leaf DE
免疫检查点抑制剂（CPI）是靶向T细胞上表达的抑制性受体的单克隆抗体，代表了一类用于治疗实体器官和血液恶性肿瘤的新兴免疫疗法。我们描述了13例接受肾活检的CPI诱导的急性肾损伤（阿基）患者的临床和组织学特征。从开始CPI到阿基的中位时间为91天（范围：21 - 245）。8例患者出现脓尿，中位尿蛋白/肌酐比值为0.48（范围：0.12 - 0.98）g/g。7例患者在阿基发作前发生肾外免疫相关不良事件。中位峰值血清肌酐为4.5（四分位距，3.6-7.3）mg/dl，4例患者需要血液透析。12例患者的主要病理改变为急性肾小管间质性肾炎，其中3例具有肉芽肿特征，1例为血栓性微血管病。在12例急性肾小管间质性肾炎患者中，10例接受糖皮质激素治疗，分别有2例和7例患者肾功能完全或部分改善。然而，2例未给予糖皮质激素的急性肾小管间质性肾炎患者肾功能无改善。因此，CPI诱导的阿基是一种新的实体，其临床和组织学特征与药物诱导的急性肾小管间质性肾炎的其他原因相似，但潜伏期较长。糖皮质激素似乎是一种潜在有效的治疗策略。因此，CPI引起阿基可能是由与免疫系统重编程相关的独特作用机制引起的，导致耐受性丧失。
Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extra-renal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and one thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the two patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance.