title: Effect of atorvastatin therapy and conversion to tacrolimus on hypercholesterolemia and endothelial dysfunction after renal transplantation.
abstract: BACKGROUND
  Hypercholesterolemia is a frequent complication in renal transplant patients treated with cyclosporine A (CsA). Whether it is preferable to treat hypercholesterolemia with statins or to switch patients from CsA to tacrolimus (TRL) has not been investigated.
  
  
  METHODS
  Twelve CsA-treated kidney transplant recipients with hypercholesterolemia were successively crossed over from CsA alone to: CsA plus atorvastatin; TRL alone; and TRL plus atorvastatin. Total cholesterol (C), Low density lipoprotein (LDL)-C, high density lipoprotein (HDL)-C, LDL and HDL alpha-tocopherol content, lag-time of LDL oxidation, plasma levels of oxidized LDL and the percentage of small dense LDL were assayed at the end of each treatment period. Endothelial function was assessed by high resolution ultrasound measurement of flow-mediated brachial artery vasodilatation (FMD).
  
  
  RESULTS
  Atorvastatin therapy was more efficient in reducing total cholesterol and LDL-C levels than conversion from CsA to TRL. Combining TRL with atorvastatin further reduced LDL-C levels as compared to TRL alone, but was no more efficient than the CsA-statin combination. Neither atorvastatin therapy nor conversion to TRL significantly changed the proportion of dense LDL, lipoprotein alpha-tocopherol contents or the lag time of LDL oxidation. Addition of atorvastatin to CsA increased FMD from 4.0+/-1.8% to 6.5+/-4.0% (P<0.05 vs. CsA). Conversion from CsA to TRL caused a slight improvement in FMD (5.1+/-2.1%, P<0.05 vs. CsA). Adding atorvastatin to TRL had no detectable effect on FMD (5.5+/-2.3%, P=NS vs. TRL).
  
  
  CONCLUSIONS
  Atorvastatin was more efficient in reducing total and LDL cholesterol levels of CsA-treated renal transplant patients than conversion to TRL and significantly improved endothelial dysfunction.
authors.affiliation: Department of Nephrology, CUB-Hopital Erasme, Brussels, Belgium. wissing@ulb.ac.be
authors.forename: Karl Martin
authors.initials: KM
authors.lastname: Wissing
authors.forename: Philippe
authors.initials: P
authors.lastname: Unger
authors.forename: Lydia
authors.initials: L
authors.lastname: Ghisdal
authors.forename: Nilufer
authors.initials: N
authors.lastname: Broeders
authors.forename: Guy
authors.initials: G
authors.lastname: Berkenboom
authors.forename: Yvon
authors.initials: Y
authors.lastname: Carpentier
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D000069059:Atorvastatin; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000453:epidemiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D008055:Lipids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin; D003404:Creatinine; D016559:Tacrolimus