Kyubok Jin1, Bong-Soo Park1, Yang-Wook Kim1, Nosratola D Vaziri2. 1. Department of Medicine, Inje University, Haeundae Paik Hospital, Busan, South Korea. 2. Department of Medicine, Division of Nephrology and Hypertension, University of California Irvine, Irvine, CA. Electronic address: ndvaziri@uci.edu.
Abstract
BACKGROUND: 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. STUDY DESIGN: 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). PREDICTOR: Group and serum total and LDL cholesterol levels. OUTCOMES: Plasma PCSK9 concentration. MEASUREMENTS: Concentrations of fasting serum PCSK9, lipids, and albumin, and urine protein excretion. RESULTS: 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). LIMITATIONS: Small number of participants may limit generalizability. CONCLUSIONS: Nephrotic syndrome and PD are associated with higher plasma PCSK9 concentration, which can contribute to elevation of LDL levels by promoting LDLR deficiency.
BACKGROUND: 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 PDpatients may be due to increased PCSK9 levels. STUDY DESIGN: 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). PREDICTOR: Group and serum total and LDL cholesterol levels. OUTCOMES: Plasma PCSK9 concentration. MEASUREMENTS: Concentrations of fasting serum PCSK9, lipids, and albumin, and urine protein excretion. RESULTS: Mean serum total and LDL cholesterol levels in patients with nephrotic syndrome (317.9±104.2 [SD] and 205.9±91.1mg/dL) and PDpatients (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 PDpatients (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). LIMITATIONS: Small number of participants may limit generalizability. CONCLUSIONS:Nephrotic syndrome and PD are associated with higher plasma PCSK9 concentration, which can contribute to elevation of LDL levels by promoting LDLR deficiency.
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