Department of Medicine, Inje University, Haeundae Paik Hospital, Busan, South Korea.
Department of Medicine, Division of Nephrology and Hypertension, University of California Irvine, Irvine, CA.
Am J Kidney Dis. 2014 Apr;63(4):584-9. doi: 10.1053/j.ajkd.2013.10.042. Epub 2013 Dec 4.
Serum total and low-density lipoprotein (LDL) cholesterol levels are elevated in patients with nephrotic syndrome and those with kidney failure treated by peritoneal dialysis (PD), who are characterized by heavy losses of protein in urine and peritoneal dialysate, respectively. Hypercholesterolemia in nephrotic syndrome is associated with and largely due to acquired LDL receptor (LDLR) deficiency. Because PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of LDLR, we tested the hypothesis that elevation of LDL cholesterol levels in patients with nephrotic syndrome and PD patients may be due to increased PCSK9 levels.
Cross-sectional study.
SETTING & PARTICIPANTS: Patients with nephrotic syndrome or treated by PD or hemodialysis and age- and sex-matched healthy Korean individuals (n=15 in each group).
Group and serum total and LDL cholesterol levels.
Plasma PCSK9 concentration.
Concentrations of fasting serum PCSK9, lipids, and albumin, and urine protein excretion.
Mean serum total and LDL cholesterol levels in patients with nephrotic syndrome (317.9±104.2 [SD] and 205.9±91.1mg/dL) and PD patients (200.0±27.6 and 126.7±18.5mg/dL) were significantly (P<0.05) higher than in hemodialysis patients (140.9±22.9 and 79.1±19.5mg/dL) and the control group (166.5±26.5 and 95.9±25.2mg/dL). This was associated with significantly (P<0.05) higher plasma PCSK9 levels in patients with nephrotic syndrome (15.13±4.99ng/mL) and PD patients (13.30±1.40ng/mL) than in the control (9.19±0.60ng/mL) and hemodialysis (7.30±0.50ng/mL) groups. Plasma PCSK9 level was directly related to total and LDL cholesterol concentrations in the study population (r=0.559 [P<0.001] and r=0.497 [P<0.001], respectively).
Small number of participants may limit generalizability.
Nephrotic syndrome and PD are associated with higher plasma PCSK9 concentration, which can contribute to elevation of LDL levels by promoting LDLR deficiency.
肾病综合征和接受腹膜透析（PD）治疗的肾衰竭患者的血清总胆固醇和低密度脂蛋白（LDL）水平升高，分别表现为尿液和腹膜透析液中大量蛋白质丢失。肾病综合征中的高胆固醇血症与 LDL 受体（LDLR）的获得性缺乏有关，并且在很大程度上是由于 LDLR 的缺乏引起的。由于 PCSK9（脯氨酸内切酶枯草溶菌素/柯萨奇蛋白酶 9）可促进 LDLR 的降解，因此我们检验了这样一种假设，即肾病综合征和 PD 患者的 LDL 胆固醇水平升高可能是由于 PCSK9 水平升高所致。
横断面研究。
肾病综合征患者或接受 PD 或血液透析治疗的患者以及年龄和性别匹配的健康韩国人（每组 15 人）。
组和血清总胆固醇及 LDL 胆固醇水平。
空腹血清 PCSK9、脂质和白蛋白浓度以及尿蛋白排泄量。
肾病综合征患者（317.9±104.2[SD]和 205.9±91.1mg/dL）和 PD 患者（200.0±27.6 和 126.7±18.5mg/dL）的血清总胆固醇和 LDL 胆固醇水平明显高于血液透析患者（140.9±22.9 和 79.1±19.5mg/dL）和对照组（166.5±26.5 和 95.9±25.2mg/dL）（P<0.05）。这与肾病综合征患者（15.13±4.99ng/mL）和 PD 患者（13.30±1.40ng/mL）的血浆 PCSK9 水平明显高于对照组（9.19±0.60ng/mL）和血液透析组（7.30±0.50ng/mL）（P<0.05）相关。研究人群中，血浆 PCSK9 水平与总胆固醇和 LDL 胆固醇浓度呈直接相关（r=0.559[P<0.001]和 r=0.497[P<0.001]）。
参与者人数少可能会限制其普遍性。
肾病综合征和 PD 与较高的血浆 PCSK9 浓度相关，这可能通过促进 LDLR 缺乏来升高 LDL 水平。
