Kynurenine, quinolinic acid--the new factors linked to carotid atherosclerosis in patients with end-stage renal disease.
Increased oxidative stress (SOX), inflammation and accelerated atherosclerosis have been reported in end-stage renal disease (ESRD), but their associations with kynurenine pathway activation remain unknown. We determined the plasma concentrations of kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA); three distinct SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD), total peroxide and malondialdehyde (MDA), high sensitivity C-reactive protein (hs CRP) as a indicator of inflammation, and intima-media thickness (IMT)--an early reflection of the systemic atherosclerosis in the population of 124 patients with ESRD. In uraemia, the concentrations of KYN, KYNA and QA were increased by 37-105%, by 84-428%, and by 394-1018% of the control values; respectively. These changes were accompanied by significant increase in kyna/kyn and qa/kyn ratios, reflecting increased activity of kynurenine pathway enzymes. KYN, QA and qa/kyn ratio were positively associated with inflammation, SOX markers, and IMT values in uraemics. Moreover, multiple stepwise regression analysis identified age, presence of diabetes mellitus, QA and qa/kyn ratio as the independent variables significantly associated with increased IMT in this population. In conclusion, the results of the present study suggest a relationship between kynurenine pathway activation and increased oxidative stress, inflammation and the progression of atherosclerosis in end-stage renal disease patients.
Pawlak
Krystyna
K
Department of Monitored Pharmacotherapy, Medical University, Bialystok, Poland.
Brzosko
Szymon
S
Mysliwiec
Michal
M
Pawlak
Dariusz
D
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology*; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D018836:Inflammation Mediators / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000628:therapy; D007736:Kynurenic Acid / Q000097:blood*; D007737:Kynurenine / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010545:Peroxides / Q000097:blood; D017378:Quinolinic Acid / Q000097:blood*; D006435:Renal Dialysis; D018570:Risk Assessment; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000097:blood; D014463:Ultrasonography; D014511:Uremia / Q000097:blood / Q000209:etiology*
D015415:Biomarkers; D018836:Inflammation Mediators; D010545:Peroxides; D007737:Kynurenine; D008315:Malondialdehyde; D002097:C-Reactive Protein; D013482:Superoxide Dismutase; D017378:Quinolinic Acid; D007736:Kynurenic Acid