Document Detail

Kynurenines and oxidative status are independently associated with thrombomodulin and von Willebrand factor levels in patients with end-stage renal disease.
MedLine Citation:
PMID:  19477487     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Increased oxidative stress (SOX) is one of the most potent inductors of endothelial dysfunction in end-stage renal disease (ESRD) patients. Kynurenines are the metabolites of tryptophan (TRP) degradation in mammals. However, the role of kynurenines in the function of the endothelium is still not recognized. MATERIALS AND METHODS: We determined the plasma concentrations of TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HKYN), quinolinic acid (QA); markers of SOX: Cu/Zn superoxide dismutase (Cu/Zn SOD), malondialdehyde (MDA); and endothelial dysfunction markers: thrombomodulin (TM) and von Willebrand factor (vWF) levels in 148 ESRD patients and healthy controls. RESULTS: TM, vWF, KYN, 3-HKYN and QA levels were significantly elevated in ESRD patients compared to controls. TRP concentrations in uremics were significantly lower than in healthy people. Both dialyzed groups showed a significant increase Cu/Zn SOD and MDA levels compared to controls. TM and vWF were positively associated with kynurenine pathway metabolites: KYN, 3-HKYN, QA (all p<0.001), and with SOX markers: Cu/Zn SOD (both p<0.0001) and MDA levels (p<0.05, and p<0.0001; respectively) in the whole ESRD group. The positive relationship were between Cu/Zn SOD and KYN (p<0.010), 3-HKYN and QA levels (both p<0.0001), whereas MDA was correlated with 3-HKYN and QA concentrations (both p<0.05). Multiple stepwise regression analysis showed that KYN metabolites and oxidative status were the independent variables significantly associated with increased both TM and vWF levels in uremic patients. CONCLUSIONS: Our study demonstrated that kynurenine metabolites and increased oxidative status are independently and significantly associated with endothelial dysfunction in ESRD patients.
Krystyna Pawlak; Tomasz Domaniewski; Michal Mysliwiec; Dariusz Pawlak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-28
Journal Detail:
Title:  Thrombosis research     Volume:  124     ISSN:  1879-2472     ISO Abbreviation:  Thromb. Res.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-31     Completed Date:  2009-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  452-7     Citation Subset:  IM    
Department of Monitored Pharmacotherapy, Medical University, Bialystok, Poland.
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MeSH Terms
Biological Markers / blood
Endothelium, Vascular / physiopathology
Kidney Failure, Chronic / blood*,  metabolism,  physiopathology
Kynurenine / blood*,  metabolism
Middle Aged
Oxidative Stress*
Reproducibility of Results
Thrombomodulin / blood*
von Willebrand Factor / analysis*
Reg. No./Substance:
0/Biological Markers; 0/Thrombomodulin; 0/von Willebrand Factor; 343-65-7/Kynurenine

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