Department of Nephrology, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China.
Department of Pathology, Fudan University School of Basic Medical Sciences, Shanghai, Shanghai, China.
J Clin Pathol. 2024 Jun 19;77(7):471-477. doi: 10.1136/jcp-2023-209173.
Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity.
We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared.
A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively).
Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.
免疫检查点抑制剂（ICPi）联合抗血管内皮生长因子（VEGF）治疗在各种恶性肿瘤中已逐渐成为一种很有前途的策略。然而，这种联合治疗可能会增加肾毒性的风险。
我们回顾性招募了接受抗 VEGF/ICPi 单药或联合治疗后发生肾损伤并接受肾活检的患者，并将其分为三组：抗 VEGF 单药治疗组、ICPi 单药治疗组和联合治疗组。分析三组患者的临床和组织病理学特征。所有患者在活检后均随访 3 个月，观察有无糖皮质激素治疗，并比较其肾脏结局。
共纳入 46 例患者。18 例患者接受抗 VEGF 单药治疗，12 例患者接受 ICPi 单药治疗，16 例患者接受抗 VEGF 和 ICPi 联合治疗。抗 VEGF 组、ICPi 组和联合组的蛋白尿水平分别为 4.07±3.17 g/d、0.60±0.61 g/d 和 2.05±2.50 g/d（p=0.002）。联合组的血清肌酐峰值水平（1.75±0.77 mg/dL）也介于 ICPi 组（2.79±0.90 mg/dL）和抗 VEGF 组（1.34±0.60 mg/dL）之间（p<0.001）。大多数联合组患者的肾脏组织病理表现为肾小球、肾小管间质和血管均受累（68.8%）。联合治疗的肾脏完全和部分恢复率也介于单药治疗之间（57.1% vs 抗 VEGF 组的 40.0%，ICPi 组为 100.0%）。
与单药治疗相比，接受 ICPi 和抗 VEGF 联合治疗的患者发生的肾损伤表现为混合性病理模式和中等临床特征。需要更大规模、更好设计的队列研究和基础研究来阐明联合抗肿瘤治疗对肾功能的“保护”作用机制。
