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慢性肾脏病中的前蛋白转化酶枯草溶菌素9

PCSK9 in chronic kidney disease.

作者信息

Pavlakou P, Liberopoulos E, Dounousi E, Elisaf M

机构信息

Department of Nephrology, Medical School, University of Ioannina, 45 110, Ioannina, Greece.

Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.

出版信息

Int Urol Nephrol. 2017 Jun;49(6):1015-1024. doi: 10.1007/s11255-017-1505-2. Epub 2017 Jan 13.

Abstract

PURPOSE

Chronic kidney disease (CKD) is accompanied by a number of secondary metabolic dysregulations, such as lipid abnormalities, presenting with unique characteristics. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have been introduced as the new era in the management of dyslipidemia with promising results in groups with refractory lipid abnormalities. Increasing number of studies investigate the possible association of PCSK9 levels with kidney function, especially with nephrotic range proteinuria, as well as its role as a prognostic cardiovascular risk marker in CKD. In this review, we discuss the existing evidence for PCSK9 levels in patient groups with nephrotic syndrome, non-dialysis CKD, end-stage renal disease and kidney transplantation.

METHODS

Online research was conducted in MEDLINE database to identify articles investigating PCSK9 in all different aspects of CKD. References from relevant studies were screened for supplementary articles.

RESULTS

Four cross-sectional studies, one secondary analysis, one publication from two independent cohort studies and one multicentre prospective cohort study assessed PCSK9 plasma levels in different subgroups of CKD patients. PCSK9 levels increase in nephrotic syndrome and have a positive correlation with proteinuria. In CKD patients, no correlation was found between PCSK9 levels and estimated GFR. Peritoneal dialysis patients have higher PCSK9 levels compared with hemodialysis and renal transplant patients as well as general population.

CONCLUSION

Accumulative evidence focuses on the possible association of PCSK9 levels with kidney function. No data are available for the administration of PCSK9 inhibitors in CKD patients. Further research will optimize knowledge on the role of PCSK9 levels and PCSK9 inhibitors in CKD.

摘要

目的

慢性肾脏病(CKD)伴有多种继发性代谢紊乱,如脂质异常,具有独特特征。前蛋白转化酶枯草溶菌素/kexin 9(PCSK9)抑制剂已作为血脂异常管理的新时代药物引入,在难治性脂质异常人群中取得了有前景的结果。越来越多的研究调查PCSK9水平与肾功能,尤其是与肾病范围蛋白尿的可能关联,以及其作为CKD患者心血管疾病预后风险标志物的作用。在本综述中,我们讨论了肾病综合征、非透析CKD、终末期肾病和肾移植患者组中PCSK9水平的现有证据。

方法

在MEDLINE数据库中进行在线研究以识别在CKD各个方面研究PCSK9的文章。筛选相关研究的参考文献以获取补充文章。

结果

四项横断面研究、一项二次分析、一项来自两项独立队列研究的出版物以及一项多中心前瞻性队列研究评估了CKD患者不同亚组中的PCSK9血浆水平。PCSK9水平在肾病综合征中升高,且与蛋白尿呈正相关。在CKD患者中,未发现PCSK9水平与估计的肾小球滤过率之间存在相关性。与血液透析患者、肾移植患者以及普通人群相比,腹膜透析患者的PCSK9水平更高。

结论

累积证据聚焦于PCSK9水平与肾功能的可能关联。目前尚无关于在CKD患者中使用PCSK9抑制剂的数据。进一步的研究将优化对PCSK9水平和PCSK9抑制剂在CKD中作用的认识。

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