{"title":"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","authors":"Verity Ramirez MD, Yongkang Zhang MD","doi":"10.1016/j.jacl.2025.04.039","DOIUrl":null,"url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>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).</div></div><div><h3>Objective/Purpose</h3><div>To highlight the efficacy of PCSK9 inhibitors in managing NS-associated hyperlipidemia.</div></div><div><h3>Methods</h3><div>A chart review was conducted.</div></div><div><h3>Results</h3><div>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.</div><div>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.</div><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e29"},"PeriodicalIF":3.6000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effective treatment of statin- and ezetimibe-resistant hyperlipidemia in a patient with active membranous nephrotic syndrome using a PCSK9 inhibitor\",\"authors\":\"Verity Ramirez MD, Yongkang Zhang MD\",\"doi\":\"10.1016/j.jacl.2025.04.039\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background/Synopsis</h3><div>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).</div></div><div><h3>Objective/Purpose</h3><div>To highlight the efficacy of PCSK9 inhibitors in managing NS-associated hyperlipidemia.</div></div><div><h3>Methods</h3><div>A chart review was conducted.</div></div><div><h3>Results</h3><div>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.</div><div>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.</div><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>\",\"PeriodicalId\":15392,\"journal\":{\"name\":\"Journal of clinical lipidology\",\"volume\":\"19 3\",\"pages\":\"Page e29\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of clinical lipidology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1933287425001151\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1933287425001151","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.