title: Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors: H
authors: H
authors: Abujrad
authors: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors: J
authors: J
authors: Mayne
authors: 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.
authors: M
authors: M
authors: Ruzicka
authors: Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors: M
authors: M
authors: Cousins
authors: Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors: A
authors: A
authors: Raymond
authors: Division of Nephrology, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors: J
authors: J
authors: Cheesman
authors: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, Ontario, Canada.
authors: M
authors: M
authors: Taljaard
authors: 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.
authors: A
authors: A
authors: Sorisky
authors: 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.
authors: K
authors: K
authors: Burns
authors: 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.
authors: T C
authors: TC
authors: Ooi
mesh_terms: D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Chronic kidney disease; Hemodialysis; LDL-C; PCSK9; Statin