title: Cellular cholesterol efflux to plasma from proteinuric patients is elevated and remains unaffected by antiproteinuric treatment.
abstract: BACKGROUND
  Lipid derangements are assumed to contribute to the elevated cardiovascular risk in proteinuric patients. The impact of proteinuria on reverse cholesterol transport (RCT) is unknown. The first step in RCT, cellular cholesterol efflux to plasma, may be altered in proteinuria, consequent to changes in pre-beta high-density lipoprotein (HDL) formation and plasma phospholipid transfer protein (PLTP) activity.
  
  
  METHODS
  In six non-diabetic male patients with nephrotic-range proteinuria and 12 matched healthy men, plasma (apo)lipoproteins, pre-beta HDL formation, PLTP activity as well as the ability of plasma to promote cholesterol efflux out of cultured human skin fibroblasts were determined. These variables were also measured in response to antiproteinuric treatment, consisting of single and dual RAAS blockade by losartan and lisinopril.
  
  
  RESULTS
  Plasma total cholesterol (P<0.05), triglycerides (P<0.05), apolipoprotein (apo) A-I (P<0.001), apo B (P<0.001), PLTP activity (P<0.005) and pre-beta HDL formation (P<0.001) were higher in proteinuric patients. Cellular cholesterol efflux to plasma from proteinuric patients was 41% higher than to plasma from healthy subjects (P<0.001). Reduction of proteinuria from 5.0 to 1.4 g/day by dual RAAS blockade was associated with a 23% reduction in plasma apo B levels (P<0.05). Pre-beta HDL formation and plasma PLTP activity did not change significantly. Combined antiproteinuric treatment did not reduce the elevated cellular cholesterol efflux.
  
  
  CONCLUSIONS
  Cellular cholesterol efflux to plasma from patients with nephrotic-range proteinuria is enhanced, in conjunction with elevated pre-beta HDL formation and plasma PLTP activity. These changes may attenuate the cardiovascular risk associated with proteinuria-associated hyperlipidaemia. Antiproteinuric therapy lowers plasma apo B, but does not affect cell-derived cholesterol efflux, suggesting that this therapy beneficially affects cardiovascular risk in proteinuric patients.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, room 4.045, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9718 NX Groningen, The Netherlands. liffertvogt@hotmail.com
authors.forename: Liffert
authors.initials: L
authors.lastname: Vogt
authors.forename: Gozewijn D
authors.initials: GD
authors.lastname: Laverman
authors.forename: Arie
authors.initials: A
authors.lastname: van Tol
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism*; D001692:Biological Transport; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis*; D007677:Kidney Function Tests; D017706:Lisinopril / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000187:drug effects / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D011507:Proteinuria / Q000097:blood / Q000175:diagnosis*; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D001053:Apolipoproteins; D008076:Cholesterol, HDL; D049294:Phospholipid Transfer Proteins; D017706:Lisinopril; D019808:Losartan