Cortazar Frank B, Marrone Kristen A, Troxell Megan L, Ralto Kenneth M, Hoenig Melanie P, Brahmer Julie R, Le Dung T, Lipson Evan J, Glezerman Ilya G, Wolchok Jedd, Cornell Lynn D, Feldman Paul, Stokes Michael B, Zapata Sarah A, Hodi F Stephen, Ott Patrick A, Yamashita Michifumi, Leaf David E
Renal Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Kidney Int. 2016 Sep;90(3):638-47. doi: 10.1016/j.kint.2016.04.008. Epub 2016 Jun 7.
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 extrarenal 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 1 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 2 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.
免疫检查点抑制剂（CPI）是一类靶向T细胞上表达的抑制性受体的单克隆抗体，是用于治疗实体器官和血液系统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（AKI）患者的临床和组织学特征。从开始使用CPI到发生AKI的中位时间为91天（范围为21至245天）。8例患者出现脓尿，尿蛋白与肌酐比值的中位数为0.48（范围为0.12至0.98）g/g。7例患者在AKI发作前发生了肾外免疫相关不良事件。血清肌酐峰值中位数为4.5（四分位间距为3.6 - 7.3）mg/dl，4例患者需要血液透析。常见的病理病变是12例患者出现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例接受了糖皮质激素治疗，分别有2例和7例患者的肾功能完全或部分改善。然而，2例未接受糖皮质激素治疗的急性肾小管间质性肾炎患者的肾功能没有改善。因此，CPI诱导的AKI是一种新的疾病实体，其临床和组织学特征与药物性急性肾小管间质性肾炎的其他病因相似，尽管潜伏期更长。糖皮质激素似乎是一种潜在有效的治疗策略。因此，CPI导致的AKI可能是由一种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。
