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

  • H. Abujrad
    Affiliations
    Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
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  • J. Mayne
    Affiliations
    Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
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  • M. Ruzicka
    Affiliations
    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
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  • M. Cousins
    Affiliations
    Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
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  • A. Raymond
    Affiliations
    Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
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  • J. Cheesman
    Affiliations
    Division of Nephrology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
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  • M. Taljaard
    Affiliations
    Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada

    Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, Ontario, Canada
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  • A. Sorisky
    Affiliations
    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
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  • K. Burns
    Affiliations
    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
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  • T.C. Ooi
    Correspondence
    Corresponding author. The Ottawa Hospital – Riverside Campus, 1967 Riverside Drive, Room 4-09, Ottawa, Ontario K1H 7W9, Canada. Tel.: +1 613 738 8400x81950; fax: +1 613 738 8396.
    Affiliations
    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
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      Highlights

      • Our data are the first quantitative analysis of PCSK9 levels in CKD-HD patients.
      • CKD-HD patients have lower PCSK9 levels than non-CKD controls.
      • CKD-HD patients have a positive correlation between serum PCSK9 and LDL-C levels.
      • Statin therapy elevates PCSK9 levels in CKD-HD patients similar to non-CKD subjects.

      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

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