Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels

H Abujrad; J Mayne; M Ruzicka; M Cousins; A Raymond; J Cheesman; M Taljaard; A Sorisky; K Burns; T C Ooi

doi:10.1016/j.atherosclerosis.2013.12.030

Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels

Atherosclerosis. 2014 Mar;233(1):123-9. doi: 10.1016/j.atherosclerosis.2013.12.030. Epub 2014 Jan 8.

Authors

H Abujrad¹, J Mayne², M Ruzicka³, M Cousins¹, A Raymond¹, J Cheesman⁴, M Taljaard⁵, A Sorisky⁶, K Burns³, T C Ooi⁷

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
² Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
³ Division of Nephrology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Chronic Disease Program, Ottawa, Ontario, Canada.
⁴ Division of Nephrology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
⁵ Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, Ontario, Canada.
⁶ Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Chronic Disease Program, Ottawa, Ontario, Canada.
⁷ Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Chronic Disease Program, Ottawa, Ontario, Canada. Electronic address: tcooi@toh.on.ca.

PMID: 24529132
DOI: 10.1016/j.atherosclerosis.2013.12.030

Abstract

Objectives: Serum low density lipoprotein-cholesterol (LDL-C) correlates positively with serum PCSK9 in the general population, consistent with PCSK9 being a determinant of LDL-C levels. Patients with chronic kidney disease (CKD) on hemodialysis (HD) have lower total cholesterol (TC) and LDL-C compared to the general population. Serum PCSK9 and its relationship with serum lipids have not been reported in CKD patients on HD (CKD-HD).

Methods: We measured serum PCSK9 by ELISA and lipid levels in 66 CKD-HD patients and compared them to 178 non-CKD subjects. Since statins increase serum PCSK9 levels, CKD-HD patients were separated into those not on statin therapy (HD-NS, n = 32) and those taking statins (HD-S, n = 34). No control subjects were on statin therapy.

Results: Serum PCSK9, TC, LDL-C and HDL-C levels were significantly lower in the CKD-HD group (n = 66) compared to the control group. HD-NS patients showed lower PCSK9, TC and LDL-C levels than control subjects and PCSK9 levels correlated with TC and LDL-C levels (r = 0.35, p = 0.050; r = 0.423, p = 0.0158 respectively) as well as TG levels (r = 0.413, p = 0.0188). In HD-S patients, PCSK9 levels were not significantly different from the non-CKD group. There was no correlation between PCSK9 levels and TC and LDL-C levels in the HD-S group.

Conclusion: Our data are the first quantitative analysis of serum PCSK9 levels in CKD-HD patients. We show that serum PCSK9 in HD-NS patients is decreased and it retains a positive correlation with LDL-C, suggesting that PCSK9 may remain a significant determinant of LDL-C in CKD-HD subjects. We also show that statin therapy disrupts the correlation between LDL-C and PCSK9 in CKD-HD patients. These data suggest that the regulation of LDL-C by PCSK9 remains intact in CKD-HD patients. PCSK9 may also play a role in the metabolism of triglyceride-rich lipoproteins in CKD-HD patients.

Keywords: Chronic kidney disease; Hemodialysis; LDL-C; PCSK9; Statin.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Cholesterol, HDL / blood
Cholesterol, LDL / blood*
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
Male
Middle Aged
Proprotein Convertase 9
Proprotein Convertases / blood*
Renal Dialysis
Renal Insufficiency, Chronic / drug therapy
Renal Insufficiency, Chronic / enzymology*
Serine Endopeptidases / blood*

Substances

Cholesterol, HDL
Cholesterol, LDL
Hydroxymethylglutaryl-CoA Reductase Inhibitors
PCSK9 protein, human
Proprotein Convertase 9
Proprotein Convertases
Serine Endopeptidases