PCSK9抑制剂有效治疗活动性膜性肾病综合征患者的他汀类和依折替米耐药高脂血症

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Verity Ramirez MD, Yongkang Zhang MD
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引用次数: 0

摘要

背景/摘要:高脂血症是肾病综合征(NS)的一个特征,有助于增加心血管风险。蛋白转化酶枯草素激酶9 (PCSK9)在NS中上调,导致脂质代谢失调。因此,PCSK9抑制剂有望成为ns相关高脂血症的治疗药物。本病例报告描述了PCSK9抑制剂在治疗活动性膜性肾病(MN)患者的他汀和依泽替米耐药高脂血症中的有效性。目的:探讨PCSK9抑制剂治疗ns相关性高脂血症的疗效。方法进行图表回顾。结果1例40岁男性mn型肾病综合征合并复发性肺栓塞、慢性血栓栓塞性肺动脉高压(CTEPH)、胰岛素依赖型糖尿病患者在大剂量他汀类药物和依折替米贝治疗后出现严重高脂血症。由于CTEPH的肺血栓栓塞切除术,他的NS免疫治疗被推迟。病人不喝酒,每天抽半包烟。由于CTEPH引起的呼吸困难,他无法运动。药物治疗前血脂指数为总胆固醇(TC) 295 mg/dL,甘油三酯(TG) 172 mg/dL,低密度脂蛋白(LDL) 195 mg/dL。在开始服用阿托伐他汀80 mg和依折替米贝10 mg后,他的血脂水平仍然升高,TC为296 mg/dL, TG为323 mg/dL, LDL为174 mg/dL。脂蛋白(a)为69 mg/dL。鉴于持续的高脂血症,他开始使用PCSK9抑制剂Evolocumab。在一个月内,他的血脂水平显著改善到TC 120 mg/dL, TG 131 mg/dL, LDL 44 mg/dL, LDL降低了74%,TG降低了59%。患者接受了计划中的肺血栓栓塞切除术,并在术后开始了NS治疗。结论:该病例强调了Evolocumab治疗尚未开始免疫治疗的活动性mn型肾病综合征患者高脂血症的疗效。先前的病例报告显示PCSK9抑制剂在他汀类药物无效的免疫治疗难治性肾病综合征中取得了类似的成功,包括日本的一份报告,其中Evolocumab在阿托伐他汀治疗的难治性最小变化疾病(MCD)患者中降低了78%的LDL。另一个病例系列显示,在12例难治性MN-、MCD-或局灶节段性肾小球硬化症(FSGS)型NS患者中,PCSK9抑制剂可使LDL降低36.8%,他汀类药物±依折替米比未达到LDL目标。我们的病例补充了现有文献,证明PCSK9抑制剂甚至在免疫治疗开始之前就可以有效地治疗nsns相关高脂血症,支持未来研究PCSK9抑制剂作为nsns相关高脂血症的有效治疗方法的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effective treatment of statin- and ezetimibe-resistant hyperlipidemia in a patient with active membranous nephrotic syndrome using a PCSK9 inhibitor

Background/Synopsis

Hyperlipidemia is a characteristic of nephrotic syndrome (NS), contributing to increased cardiovascular risk. Proprotein convertase subtilisin kexin 9 (PCSK9) is upregulated in NS, leading to dysregulated lipid metabolism. Consequently, PCSK9 inhibitors are emerging as promising therapeutic agents for NS-associated hyperlipidemia. This case report describes the effectiveness of a PCSK9 inhibitor in treating statin- and ezetimibe-resistant hyperlipidemia in a patient with active membranous nephropathy (MN).

Objective/Purpose

To highlight the efficacy of PCSK9 inhibitors in managing NS-associated hyperlipidemia.

Methods

A chart review was conducted.

Results

A 40-year-old male with MN-type nephrotic syndrome complicated by recurrent pulmonary emboli and chronic thromboembolic pulmonary hypertension (CTEPH), and insulin-dependent diabetes presented with severe hyperlipidemia on high-dose statin and ezetimibe. His immunotherapy for NS was delayed due to a planned pulmonary thromboembolectomy for CTEPH.
The patient did not drink alcohol and smoked half a pack of cigarettes daily. He was unable to exercise due to dyspnea from CTEPH. His lipid panel before medical therapy was total cholesterol (TC) 295 mg/dL, triglycerides (TG) 172 mg/dL, and LDL 195 mg/dL. After initiation of atorvastatin 80 mg and ezetimibe 10 mg, his lipid panel remained elevated with TC 296 mg/dL, TG 323 mg/dL, and LDL 174 mg/dL. Lipoprotein(a) was 69 mg/dL.
Given persistent hyperlipidemia, he was started on the PCSK9 inhibitor Evolocumab. Within one month, his lipid profile dramatically improved to TC 120 mg/dL, TG 131 mg/dL, and LDL 44 mg/dL, representing a 74% reduction in LDL and 59% reduction in TG. The patient underwent planned pulmonary thromboembolectomy and started NS treatment post-surgery.

Conclusions

This case highlights the efficacy of Evolocumab in managing hyperlipidemia in a patient with active MN-type nephrotic syndrome who had not yet started immunotherapy. Previous case reports have shown similar successes with PCSK9 inhibitors in immunotherapy-refractory nephrotic syndrome not responding to statins, including a Japanese report where Evolocumab reduced LDL by 78% in a patient with refractory minimal change disease (MCD) on atorvastatin. Another case series showed a 36.8% reduction in LDL with PCSK9 inhibitors in 12 patients with refractory MN-, MCD-, or focal segmental glomerulosclerosis (FSGS)-type NS not at LDL goal with statin ± ezetimibe. Our case adds to the existing literature by demonstrating that PCSK9 inhibitors can effectively treat NS-associated hyperlipidemia even before immunotherapy initiation, supporting the need for future studies on PCSK9 inhibitors as a potent therapeutic for NS-associated hyperlipidemia.
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来源期刊
CiteScore
7.00
自引率
6.80%
发文量
209
审稿时长
49 days
期刊介绍: Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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