Abstract

Background 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. Methods One hundred and sixteen patients who were newly diagnosed with PNS were enrolled in this study. Results 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, p = 0.002]. Plasma PCSK9 in PNS patients was positively correlated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (γ = 0.246, p = 0.008, and γ = 0.183, p = 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, p = 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, p = 0.018). Conclusions 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.

Highlights

  • Nephrotic syndrome (NS) is one of the most common clinical syndromes in terms of glomerular diseases

  • Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TG, very low-density lipoprotein cholesterol (VLDL-C), Cr, blood urea nitrogen (BUN), and uric acid (UA) were significantly higher and ALB and estimated glomerular filtration rate (eGFR) levels were significantly lower in the primary nephrotic syndrome (PNS) patients compared with those in the healthy controls (p < 0.05)

  • ELISA results showed that plasma Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in PNS patients were significantly higher than in healthy controls [310.86 (250.87, 390.25) ng/ml vs. 255.67

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Summary

Introduction

Nephrotic syndrome (NS) is one of the most common clinical syndromes in terms of glomerular diseases. Plasma PCSK9 in PNS patients was positively correlated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (c 1⁄4 0.246, p 1⁄4 0.008, and c 1⁄4 0.183, p 1⁄4 0.049). When plasma PCSK9 was >267.60 ng/ml, the risk of developing hypercholesterolemia significantly increased in PNS patients (OR 1⁄4 6.40, 95% CI 2.06–19.87, p 1⁄4 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 1⁄4 3.83, 95%CI 1.25–11.68, p 1⁄4 0.018). Conclusions: 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

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