Shen Huaying, Feng Sheng, Lu Ying, Jiang Linsen, Yang Tingting, Wang Zhi
Department of Nephrology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Ren Fail. 2020 Nov;42(1):405-412. doi: 10.1080/0886022X.2020.1756846.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major post-transcriptional regulator of low-density lipoprotein receptor degradation. Recently, PCSK9 was shown to be overexpressed by liver cells in rats with proteinuria. However, the levels of PCSK9 in newly diagnosed primary nephrotic syndrome (PNS) patients and correlations involving PCSK9 and blood lipids are not clearly understood. One hundred and sixteen patients who were newly diagnosed with PNS were enrolled in this study. Plasma PCSK9 levels in PNS patients were significantly higher than those in healthy controls [310.86 (250.87, 390.25) ng/ml vs 255.67 (202.26, 320.26) ng/ml, = 0.002]. Plasma PCSK9 in PNS patients was positively correlated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (γ = 0.246, = 0.008, and = 0.183, = 0.049). When plasma PCSK9 was >267.60 ng/ml, the risk of developing hypercholesterolemia significantly increased in PNS patients (OR = 6.40, 95% CI 2.06-19.87, = 0.001). When plasma PCSK9 was >255.05 ng/ml, the risk of developing higher levels of LDL-C significantly increased in PNS patients (OR = 3.83, 95%CI 1.25-11.68, = 0.018). Plasma PCSK9 levels in newly diagnosed PNS patients were markedly increased, and elevated PCSK9 abundance was positively correlated with elevated serum TC and LDL-C levels, suggesting that PCSK9 may emerge as a novel therapeutic target in NS-associated hypercholesterolemia.
前蛋白转化酶枯草溶菌素/kexin 9型(PCSK9)是低密度脂蛋白受体降解的主要转录后调节因子。最近研究表明,蛋白尿大鼠的肝细胞中PCSK9表达上调。然而,新诊断的原发性肾病综合征(PNS)患者的PCSK9水平以及PCSK9与血脂之间的相关性尚不清楚。本研究纳入了116例新诊断为PNS的患者。PNS患者的血浆PCSK9水平显著高于健康对照组[310.86(250.87,390.25)ng/ml对255.67(202.26,320.26)ng/ml,P = 0.002]。PNS患者血浆PCSK9与总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)呈正相关(γ = 0.246,P = 0.008,以及γ = 0.183,P = 0.049)。当血浆PCSK9>267.60 ng/ml时,PNS患者发生高胆固醇血症的风险显著增加(OR = 6.40,95%CI 2.06 - 19.87,P = 0.001)。当血浆PCSK9>255.05 ng/ml时,PNS患者LDL-C水平升高的风险显著增加(OR = 3.83,95%CI 1.25 - 11.68,P = 0.018)。新诊断的PNS患者血浆PCSK9水平显著升高,PCSK9丰度升高与血清TC和LDL-C水平升高呈正相关,提示PCSK9可能成为NS相关高胆固醇血症的新型治疗靶点。