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抗程序性死亡受体-1 治疗晚期黑色素瘤患者的急性肾损伤:单中心队列的真实研究。

Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort.

机构信息

Assistance Publique-Hôpitaux de Marseille, Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Marseille, France.

Aix-Marseille University, INSERM 1263, INRAE 1260, Centre de recherche en CardioVasculaire et Nutrition, Marseille, France.

出版信息

Nephrol Dial Transplant. 2021 Aug 27;36(9):1664-1674. doi: 10.1093/ndt/gfaa137.

Abstract

BACKGROUND

Immune checkpoints inhibitors have transformed the prognosis of advanced melanoma but are associated with immune-related adverse events (irAEs). We evaluated the incidence, risk factors and causes of acute kidney injury (AKI) in a monocentric real-life cohort of patients treated with anti-programmed death receptor-1 (anti-PD1) antibodies for advanced melanoma.

METHODS

Retrospective collection of medical charts and comprehensive analysis of lab results from patients treated with nivolumab or pembrolizumab for advanced melanoma between 2014 and 2018 was carried out. AKI was defined by Kidney Disease Improving Global Outcomes criteria, and causes were determined by chart review. Overall survival, survival without AKI and impact of AKI on survival were analysed. Risk factors for death and for AKI were identified.

RESULTS

Two hundred and thirty-nine patients were included. Forty-one (17%) had at least one episode of AKI. Independent risk factors for AKI were treatment with renin-angiotensin-aldosterone system inhibitors (RAASi), pre-existing chronic kidney disease (CKD) and cumulated doses of anti-PD1. The main cause of AKI was prerenal, and only eight patients (3.3%) developed acute interstitial nephritis; 8% of patients developed CKD. The median overall survival was 13.4 months and was not affected by AKI. In multivariate analysis, the overall mortality was lower in overweight and obese patients and higher in patients treated with proton-pump inhibitors (PPI) or corticosteroids.

CONCLUSIONS

AKI is common in patients treated with anti-PD1 for advanced melanoma but is mostly prerenal and favoured by the use of RAASi; renal irAE is rare. PPI and corticosteroids were associated with poor survival in this population, while overweight/obesity was protective.

摘要

背景

免疫检查点抑制剂改变了晚期黑色素瘤的预后,但与免疫相关的不良反应(irAEs)有关。我们评估了抗程序性死亡受体-1(抗 PD1)抗体治疗晚期黑色素瘤患者的单中心真实队列中急性肾损伤(AKI)的发生率、危险因素和原因。

方法

回顾性收集了 2014 年至 2018 年间接受纳武单抗或帕博利珠单抗治疗的晚期黑色素瘤患者的病历和综合实验室结果,并进行了分析。根据肾脏病改善全球结局(KDIGO)标准定义 AKI,并通过病历回顾确定病因。分析了总生存期、无 AKI 生存期和 AKI 对生存期的影响。确定了死亡和 AKI 的危险因素。

结果

共纳入 239 例患者。41 例(17%)至少发生过一次 AKI。AKI 的独立危险因素包括使用肾素-血管紧张素-醛固酮系统抑制剂(RAASi)、预先存在的慢性肾脏病(CKD)和累积 PD1 剂量。AKI 的主要病因是肾前性,仅有 8 例(3.3%)患者发生急性间质性肾炎;8%的患者发生 CKD。中位总生存期为 13.4 个月,不受 AKI 的影响。多变量分析显示,超重和肥胖患者的总体死亡率较低,而使用质子泵抑制剂(PPI)或皮质类固醇的患者死亡率较高。

结论

抗 PD1 治疗晚期黑色素瘤患者中 AKI 很常见,但大多是肾前性的,RAASi 的使用更易导致 AKI;肾免疫相关不良反应罕见。在该人群中,PPI 和皮质类固醇与不良预后相关,而超重/肥胖则具有保护作用。

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