Proprotein convertase subtilisin-kexin type 9 is elevated in proteinuric subjects: Relationship with lipoprotein response to antiproteinuric treatment

被引：45

作者：

Kwakernaak, Arjan J. ^{[1
]}

Lambert, Gilles ^{[2
,3
]}

Slagman, Maartje C. J. ^{[1
]}

Waanders, Femke ^{[1
]}

Laverman, Gozewijn D. ^{[4
]}

Petrides, Francine ^{[2
]}

Dikkeschei, Bert D. ^{[5
]}

Navis, Gerjan ^{[1
]}

Dullaart, Robin P. F. ^{[6
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Med, NL-9700 RB Groningen, Netherlands

[2] Heart Res Inst, Sydney, NSW, Australia

[3] Univ Nantes, Fac Med, INSERM, U957, Nantes, France

[4] ZGT Hosp, Dept Med, Div Nephrol, Almelo, Netherlands

[5] Isala Clin, Dept Clin Chem, Zwolle, Netherlands

[6] Univ Groningen, Univ Med Ctr Groningen, Div Endocrinol, Dept Med, NL-9700 RB Groningen, Netherlands

来源：

ATHEROSCLEROSIS | 2013年 / 226卷 / 02期

关键词：

Antiproteinuric treatment; LDL cholesterol; Non-HDL cholesterol; Proteinuria; Proprotein convertase subtilisin-kexin type 9; Chronic kidney disease; PLASMA PCSK9 LEVELS; NEPHROTIC SYNDROME; LDL-CHOLESTEROL; CARDIOVASCULAR EVENTS; DIABETIC-PATIENTS; CONTROLLED-TRIAL; DIETARY-SODIUM; ATORVASTATIN; METABOLISM; HEMODIALYSIS;

D O I：

10.1016/j.atherosclerosis.2012.11.009

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: LDL-receptor deficiency may provide a mechanism which contributes to atherogenic lipoprotein abnormalities in experimental nephrosis and in humans with glomerular proteinuria. The proprotein convertase subtilisin-kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation. We tested whether plasma PCSK9 is elevated in proteinuric states, and determined relationships of PCSK9 with lipoprotein responses to proteinuria reduction. Methods: Thirty-nine kidney patients (e-GFR 61 +/- 29 mL/min/1.73 m(2), proteinuria 1.9 [0.9-3.3] g/day; 19 on statin treatment) were studied during 2 randomized double-blind 6-week periods on either lisinopril (40 mg/day) and a regular sodium diet (194 +/- 49 mmol Na+/day; baseline treatment) or lisinopril plus valsartan (320 mg/day) and a low sodium diet (102 +/- 52 mmol Na+/day; maximal treatment), and compared to age- and sex-matched controls. Maximal treatment decreased proteinuria to 0.5 [0.3-1.1] g/day (P < 0.001). Results: Plasma PCSK9 was increased at baseline in proteinuric subjects (213 [161-314] vs. 143 [113-190] ug/L in controls, P <= 0.001), irrespective of statin use, e-GFR and BMI. PCSK9 correlated with proteinuria at baseline (R = 0.399, P = 0.018) and at maximal antiproteinuric treatment (R = 0.525, P = 0.001), but did not decrease during proteinuria reduction (P = 0.84). Individual changes in total cholesterol (R = 0.365, P = 0.024), non-HDL cholesterol (R = 0.333, P = 0.041), and LDL cholesterol (R = 0.346, P = 0.033) were correlated positively with individual PCSK9 responses. PCSK9 at baseline independently predicted the total/HDL cholesterol ratio response to treatment (P = 0.04). Conclusion: Plasma PCSK9 was elevated in proteinuria, predicted lipoprotein responses to proteinuria reduction but remained unchanged after proteinuria reduction. Inhibition of the PCSK9 pathway may provide a novel treatment strategy in proteinuric subjects. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：459 / 465

页数：7