title: Dysfunctional high-density lipoproteins in children with chronic kidney disease.
abstract: OBJECTIVE
  Our aim was to determine if chronic kidney disease (CKD) occurring in childhood impairs the normally vasoprotective functions of high-density lipoproteins (HDLs).
  
  
  METHODS
  HDLs were isolated from children with end-stage renal disease on dialysis (ESRD), children with moderate CKD and controls with normal kidney function. Macrophage response to HDLs was studied as expression of inflammatory markers (MCP-1, TNF-α, IL-1β) and chemotaxis. Human umbilical vein endothelial cells were used for expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and adhesion. Cellular proliferation, apoptosis, and necrosis of endothelial cells were measured by MTS/PMS reagent-based assay, flow cytometry, and ELISA. Cholesterol efflux was assessed by gas chromatographic measurements of cholesterol in macrophages exposed to HDLs.
  
  
  RESULTS
  Compared with HDL(Control), HDL(CKD) and HDL(ESRD) heightened the cytokine response and disrupted macrophage chemotaxis. HDL(Control) reduced endothelial expression of ICAM-1, VCAM-1, E-selectin, whereas HDL(CKD) and HDL(ESRD) were less effective and showed reduced capacity to protect endothelial cells against monocyte adhesion. Compared with a dramatically enhanced endothelial proliferation following injurious stimulus by HDL(Control), neither HDL(CKD) nor HDL(ESRD) caused proliferative effects. HDLs of all three groups were equally protective against apoptosis assessed by flow cytometry and cleaved caspase-3 activity. Compared to HDL(Control), HDL(CKD) and HDL(ESRD) trended toward reduced capacity as cholesterol acceptors.
  
  
  CONCLUSIONS
  CKD in children impairs HDL function. Even in the absence of long-standing and concomitant risk factors, CKD alters specific HDL functions linked to control of inflammation and endothelial responses.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kaseda
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Kathy
authors.initials: K
authors.lastname: Jabs
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Tracy E
authors.initials: TE
authors.lastname: Hunley
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Deborah
authors.initials: D
authors.lastname: Jones
authors.affiliation: Department of Statistics, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Aihua
authors.initials: A
authors.lastname: Bian
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Allen
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Kasey C
authors.initials: KC
authors.lastname: Vickers
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Yancey
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Pathology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN. Electronic address: valentina.kon@vanderbilt.edu.
authors.forename: Valentina
authors.initials: V
authors.lastname: Kon
mesh_terms: D000293:Adolescent; D017209:Apoptosis; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007223:Infant; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D013714:Tennessee / Q000453:epidemiology
chemical_list: D008075:Lipoproteins, HDL; D002784:Cholesterol
keywords: CKD; Child; Endothelial cell; HDL; Macrophage