title: Impact of cholesterol lowering treatment on plasma kynurenine and tryptophan concentrations in chronic kidney disease: relationship with oxidative stress improvement.
abstract: OBJECTIVE
  Tryptophan (Trp) degradation via indoleamine (2,3)-dioxygenase (IDO), with consequent increased in kynurenine (Kyn) concentrations, has been proposed as marker of immune system activation. Oxidative stress (OS) might contribute to the pro-inflammatory state in chronic kidney disease (CKD) through the activation of NF-kB, with consequent activation and recruitment of immune cells.
  
  
  RESULTS
  Serum concentrations of Trp and Kyn, oxidative stress indices malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio and anti-oxidant amino acid taurine were measured in 30 CKD patients randomized to 40 mg/day simvastatin (group 1), ezetimibe/simvastatin 10/20 mg/day (group 2) or ezetimibe/simvastatin 10/40 mg/day (group 3) and treated for 12 months. Baseline Kyn and Kyn/Trp ratio were higher in CKD patients vs. healthy controls (1.67 ± 0.62 μmol/L vs 1.25 ± 0.40 μmol/L, p < 0.01 and 0.036 ± 0.016 vs 0.023 ± 0.010, p < 0.001 respectively). Both Kyn and Kyn/Trp ratio significantly decreased after cholesterol lowering treatment, to values comparable with healthy controls after one year treatment (1.67 ± 0.62 μmol/L vs 1.31 ± 0.51 μmol/L, p < 0.0001 and 0.036 ± 0.016 vs 0.028 ± 0.012 p < 0.0001, respectively). This was paralleled by a significant decrease in MDA (218 ± 143 nmol/L vs 176 ± 123 nmol/L, p < 0.01) and All/UA ratio (1.47 ± 0.72 vs 1.19 ± 0.51, p < 0.01) in CKD patients.
  
  
  CONCLUSIONS
  Amelioration of both oxidative and inflammation status after cholesterol lowering treatment in CKD might be mediated by restoration of antioxidant taurine concentrations during therapy (from 51.1 ± 13.3 μmol/L at baseline to 63.1 ± 16.4 μmol/L, p < 0.001 by ANOVA), suggesting that improvement of both oxidative and inflammation status in CKD patients could be explained, at least partly, by the cholesterol lowering effects.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy. Electronic address: azinellu@uniss.it.
authors.forename: A
authors.initials: A
authors.lastname: Zinellu
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sotgia
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia.
authors.forename: A A
authors.initials: AA
authors.lastname: Mangoni
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sanna
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari, Italy.
authors.forename: A E
authors.initials: AE
authors.lastname: Satta
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy; Quality Control Unit, Hospital University of Sassari (AOU), Sassari, Italy. Electronic address: carru@uniss.it.
authors.forename: C
authors.initials: C
authors.lastname: Carru
mesh_terms: D000368:Aged; D000481:Allantoin / Q000097:blood; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000069438:Ezetimibe / Q000494:pharmacology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000188:drug therapy; D019821:Simvastatin / Q000494:pharmacology; D013654:Taurine / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014364:Tryptophan / Q000097:blood*; D014527:Uric Acid / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D016328:NF-kappa B; D014280:Triglycerides; D013654:Taurine; D014527:Uric Acid; D007737:Kynurenine; D000481:Allantoin; D008315:Malondialdehyde; D014364:Tryptophan; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Chronic kidney disease; Inflammation; Kynurenine; Oxidative stress; Tryptophan