title: Dysfunctional high-density lipoprotein in patients on chronic hemodialysis.
abstract: OBJECTIVE
  This study examined the functionality of high-density lipoprotein (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD).
  
  
  BACKGROUND
  The high rate of cardiovascular disease (CVD) in chronic kidney disease is not explained by standard risk factors, especially in patients with ESRD-HD who appear resistant to benefits of statin therapy. HDL is antiatherogenic because it extracts tissue cholesterol and reduces inflammation.
  
  
  METHODS
  Cellular cholesterol efflux and inflammatory response were assessed in macrophages exposed to HDL of patients with ESRD-HD or controls.
  
  
  RESULTS
  HDL from patients with ESRD-HD was dramatically less effective than normal HDL in accepting cholesterol from macrophages (median 6.9%; interquartile range [IQR]: 1.4% to 10.2%) versus control (median 14.9%; IQR: 9.8% to 17.8%; p < 0.001). The profound efflux impairment was also seen in patients with ESRD-HD and diabetes compared with patients with diabetes without renal disease (median 8.1%; IQR: 3.3% to 12.9%) versus control (median 13.6%; IQR: 11.0% to 15.9%; p = 0.009). In vitro activation of cellular cholesterol transporters increased cholesterol efflux to both normal and uremic HDL. HDL of patients with ESRD-HD had reduced antichemotactic ability and increased macrophage cytokine response (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). HDL of patients with ESRD-HD on statin therapy had reduced inflammatory response while maintaining impaired cholesterol acceptor function. Interestingly, impaired HDL-mediated efflux did not correlate with circulating C-reactive protein levels or cellular inflammatory response.
  
  
  CONCLUSIONS
  These findings suggest that abnormal HDL capacity to mediate cholesterol efflux is a key driver of excess CVD in patients on chronic hemodialysis and may explain why statins have limited effect to decrease CV events. The findings also suggest cellular cholesterol transporters as potential therapeutic targets to decrease CV risk in this population.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Yancey
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.forename: W Gray
authors.initials: WG
authors.lastname: Jerome
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kaseda
authors.forename: Brian
authors.initials: B
authors.lastname: Cox
authors.forename: Aihua
authors.initials: A
authors.lastname: Bian
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Macrae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.forename: Valentina
authors.initials: V
authors.lastname: Kon
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000209:etiology*; D050171:Dyslipidemias / Q000097:blood / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D013997:Time Factors
chemical_list: D008075:Lipoproteins, HDL