De Giglio Andrea, Grandinetti Valeria, Aprile Marta, Borelli Greta, Campus Anita, Croci Chiocchini Anna Laura, Busutti Marco, Vischini Gisella, Di Federico Alessandro, Sperandi Francesca, Melotti Barbara, Ardizzoni Andrea, La Manna Gaetano, Gelsomino Francesco
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Nephrology, Dialysis and Renal Transplant Unit, IRCCS-Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Lung Cancer. 2022 Dec;174:91-96. doi: 10.1016/j.lungcan.2022.10.007. Epub 2022 Nov 2.
The combination of immune-checkpoint inhibitors (ICI) and platinum-pemetrexed chemotherapy (CT) in first-line setting improved survival outcomes of advanced non-small cell lung cancer (NSCLC) patients. Among the various adverse events, renal toxicity can be a relevant safety issue.
We conducted a single-center, observational retrospective study including consecutive patients treated with upfront CT-ICI for advanced nonsquamous NSCLC to investigate incidence and clinical characteristics of acute kidney injury (AKI) using 'Acute Kidney Injury Working Group of Kidney Disease: Improving Global Outcomes' (KDIGO) definition.
A total of 89 patients received a first-line CT/ICI. The median age was 69 years. 60.7 % were male, and 87.6 % had an ECOG PS of 0-1. 92.1 % had a baseline glomerular filtration rate of at least 60 ml/min. According to KDIGO criteria, 25 (28 %) patients developed AKI. Considering risk factors for AKI onset, patients receiving >10 cycles of CT/ICI were more likely to experience AKI (p < 0.001). No other associations were found with other variables, including concomitant medications. Any component of the treatment was discontinued (pemetrexed pembrolizumab or both) in 10 (40 %) patients, and 9 patients (36 %) were addressed to nephrological consultation. These patients had higher mean creatinine variation from baseline (1 vs 0.6 mg/dl, p = 0.025) and creatine level (1.8 vs 1.4 mg/dl, p = 0.015), but lower eGFR (35.7 vs 54.2 ml/min, p = 0.011) in comparison to patients not addressed. No patients had microscopic hematuria or pyuria, but mild proteinuria (<0.8 g/24 h) was found in 4 patients. A renal biopsy was performed on 3 patients, revealing acute tubule interstitial nephritis (ATIN), karyomegalic interstitial nephritis, and acute tubular necrosis (ATN).
Renal toxicity represents a challenging adverse event that could negatively impact outcomes of metastatic nonsquamous NSCLC patients receiving CT/ICI demanding a multidisciplinary approach.
一线使用免疫检查点抑制剂（ICI）与铂类培美曲塞化疗（CT）联合治疗可改善晚期非小细胞肺癌（NSCLC）患者的生存结局。在各种不良事件中，肾毒性可能是一个相关的安全问题。
我们进行了一项单中心观察性回顾性研究，纳入连续接受一线CT-ICI治疗的晚期非鳞状NSCLC患者，使用“改善全球肾脏病预后组织急性肾损伤工作组”（KDIGO）的定义来调查急性肾损伤（AKI）的发生率和临床特征。
共有89例患者接受一线CT/ICI治疗。中位年龄为69岁。60.7%为男性，87.6%的东部肿瘤协作组体能状态（ECOG PS）为0 - 1。92.1%患者的基线肾小球滤过率至少为60 ml/min。根据KDIGO标准，25例（28%）患者发生AKI。考虑到AKI发生的危险因素，接受>10周期CT/ICI治疗的患者更易发生AKI（p < 0.001）。未发现与其他变量（包括合并用药）有其他关联。10例（40%）患者停用了治疗的任何成分（培美曲塞、帕博利珠单抗或两者均停用），9例（36%）患者接受了肾脏科会诊。与未接受会诊的患者相比，这些患者的平均肌酐较基线变化更大（1 vs 0.6 mg/dl，p = 0.025）、肌酐水平更高（1.8 vs 1.4 mg/dl，p = 0.015），但估算肾小球滤过率（eGFR）更低（35.7 vs 54.2 ml/min，p = 0.011）。无患者出现镜下血尿或脓尿，但4例患者发现轻度蛋白尿（<0.8 g/24 h）。对3例患者进行了肾活检，结果显示为急性肾小管间质性肾炎（ATIN）、核肿大性间质性肾炎和急性肾小管坏死（ATN）。
肾毒性是一个具有挑战性的不良事件，可能会对接受CT/ICI治疗的转移性非鳞状NSCLC患者的结局产生负面影响，需要多学科方法应对。
