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Impact of cholesterol lowering treatment on plasma kynurenine and tryptophan concentrations in chronic kidney disease: relationship with oxidative stress improvement

Zinellu, Angelo and Sotgia, Salvatore and Mangoni, Arduino A. and Sanna, Manuela and Satta, Andrea Ercole and Carru, Ciriaco (2015) Impact of cholesterol lowering treatment on plasma kynurenine and tryptophan concentrations in chronic kidney disease: relationship with oxidative stress improvement. Nutrition, metabolism and cardiovascular diseases, Vol. 25 (2), p. 153-159. ISSN 0939-4753. eISSN 1590-3729. Article.

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DOI: 10.1016/j.numecd.2014.11.004

Abstract

Background and aim: 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 proinflammatory state in chronic kidney disease (CKD) through the activation of NF-kB, with consequent activation and recruitment of immune cells.
Methods and 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 mmol/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 6lt; 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.

Item Type:Article
ID Code:10666
Status:Published
Refereed:Yes
Uncontrolled Keywords:Chronic kidney, disease, inflammation, kynurenine, oxidative stress, tryptophan
Subjects:Area 05 - Scienze biologiche > BIO/12 Biochimica clinica e biologia molecolare clinica
Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Chirurgiche, Microchirurgiche e Mediche
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Elsevier
ISSN:0939-4753
eISSN:1590-3729
Deposited On:21 Jan 2015 15:08

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