帕博利珠单抗联合阿帕替尼致肝癌患者肾病综合征1例伴文献复习

Nephrotic syndrome caused by pembrolizumab combined with apatinib in a patient with liver carcinoma:a case report and literature review

本文报道1例由程序性死亡受体1(Programmed death receptor 1,PD-1)抑制剂和血管内皮生长因子(Vascular endothelial growth factor,VEGF)拮抗剂导致的肾病综合征。患者为72岁男性,因原发性肝癌给予PD-1抑制剂帕博利珠单抗和VEGF拮抗剂阿帕替尼联合治疗。应用PD-1抑制剂5周、VEGF拮抗剂2周后出现蛋白尿,之后进一步发展为肾病综合征。停药6周后完全缓解。肾病综合征的出现在时间上与PD-1抑制剂帕博利珠单抗和VEGF拮抗剂阿帕替尼有关。蛋白尿为阿帕替尼常见不良反应,但肾病综合征少见。本文结合文献复习进行讨论。在应用VEGF拮抗剂治疗过程中,若出现水肿、泡沫尿等情况,需警惕肾病综合征的可能性,及时发现、采用正确的治疗措施及规律的随诊对保证患者安全、改善预后具有重要的临床意义。

A case of nephrotic syndrome was reported in this article,which was caused by programmed death receptor 1(PD-1)inhibitor and vascular endothelial growth factor(VEGF)inhibitor.This patient was a 72-year-old man with primary liver cancer who received the combined therapy of PD-1 inhibitor pembrolizumab and VEGF inhibitor apatinib.After 5 weeks of treatment with pembrolizumab and 2 weeks of treatment with apatinib,he presented with proteinuria,which then progressed to nephrotic syndrome.By stopping the two medications,the patient got a complete remission six weeks later.There was a clear temporal correlation between the occurrence of nephrotic syndrome and the application of PD-1 inhibitor and anti-VEGF agents in this patient.Proteinuria is a common adverse reaction to apatinib,but nephrotic syndrome is rare.This article will give a detailed analysis based on literature review.This case reminds us of the possibility of nephrotic syndrome when patients suffer from edema and proteinuria during the process of VEGF inhibitor treatment.Correct diagnosis,proper therapy,and regular follow-up are important to ensure the patients′safety,and improve their prognosis.