Kynurenine pathway – a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients

Pawlak, Krystyna; Myśliwiec, Michał; Pawlak, Dariusz

doi:10.2478/v10039-010-0015-6

Cited by 82 publications

(72 citation statements)

References 37 publications

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“…This ratio is thought to reflect the degradation of tryptophan by the inducible enzyme indoleamine 2,3-dioxygenase, which was reported to associate cross-sectionally with CKD severity, uremic symptoms, inflammation, obesity, blood pressure and atherosclerosis [18][19][20][21]. The direction of the association for the kynurenine-to-tryptophan ratio with loss of eGFR and higher disease incidence found in our longitudinal analyses are thus in accordance with prior studies published by other investigators.…”

Section: Discussionsupporting

confidence: 82%

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population

Goek

Prehn

Sekula

et al. 2013

Nephrology Dialysis Transplantation

118

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Section: Discussionsupporting

confidence: 82%

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population

Goek

Prehn

Sekula

et al. 2013

Nephrology Dialysis Transplantation

118

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“…While these TM levels are probably too low to have a significant impact on coagulation processes, the consistent elevation in circulating TM levels during pathologies is now widely regarded as an important circulatory biomarker for endothelial dysfunction and vascular risk assessment (15). Consistent with this notion, elevated plasma TM levels have been found to correlate with atherosclerosis (119,158), cardioembolic stroke (38), obesity (165), Lupus erythomatosus-associated metabolic syndrome (105), preeclampsia (130), sepsis-associated disseminated intravascular coagulation (DIC) (90), and severe acute respiratory syndrome (SARS) (91). Significantly elevated plasma TM levels have also been observed in patients following coronary artery bypass graft (CABG) surgery (10,78).…”

Section: Posttranslational Regulationmentioning

confidence: 68%

Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects

Martin

Murphy

Cummins

2013

American Journal of Physiology-Heart and Circulatory Physiology

179

163

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“…HK correlated with intima media thickness of the carotids. 15 Moreover, HK and KA were both associated with the presence of cardiovascular disease in patients with renal failure. 16 Interestingly, a recent metabolomics study reported correlations of kynurenines with components of the metabolic syndrome 17 and hypothesized these metabolites to be involved in the pathogenesis of insulin resistance.…”

Section: Discussion Principal Findingsmentioning

confidence: 99%

Associations of Plasma Kynurenines With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris

Pedersen

Tuseth

Eussen

et al. 2015

ATVB

148

106

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Objective-Enhanced tryptophan degradation, induced by the proinflammatory cytokine interferon-γ, has been related to cardiovascular disease progression and insulin resistance. We assessed downstream tryptophan metabolites of the kynurenine pathway as predictors of acute myocardial infarction in patients with suspected stable angina pectoris. Furthermore, we evaluated potential effect modifications according to diagnoses of pre-diabetes mellitus or diabetes mellitus. Approach and Results-Blood samples were obtained from 4122 patients (median age, 62 years; 72% men) who underwent elective coronary angiography. During median follow-up of 56 months, 8.3% had acute myocardial infarction. Comparing the highest quartile to the lowest, for the total cohort, multivariable adjusted hazard ratios (95% confidence intervals) were 1.68 (1.21-2.34), 1.81 (1.33-2.48), 1.68 (1.21-2.32), and 1.48 (1.10-1.99) for kynurenic acid, hydroxykynurenine, anthranilic acid, and hydroxyanthranilic acid, respectively. The kynurenines correlated with phenotypes of the metabolic syndrome, and risk associations were generally stronger in subgroups classified with pre-diabetes mellitus or diabetes mellitus at inclusion (P int ≤0.05). Evaluated in the total population, hydroxykynurenine and anthranilic acid provided statistically significant net reclassification improvements ( Experimental studies suggest that dysregulation of the Kyn pathway may be involved in the pathogenesis of both CAD 11 and DM. 12 However, Trp catabolites other than Kyn have been related only to a limited extent to clinical outcomes in humans, and there is a paucity of data from large-scale epidemiological studies. Thus, we evaluated plasma levels of kynurenic acid (KA) hydroxykynurenine (HK), anthranilic acid (AA), xanthurenic acid, and hydroxyanthranilic acid (HAA) as predictors of AMI in a prospective cohort of patients with suspected stable angina pectoris. In particular, we were interested in whether any associations with adverse prognosis were modified by evidence of impaired glucose homeostasis. Materials and MethodsMaterials and methods are available in the online-only Data Supplement. ResultsFor the 4122 patients in the current study, median (25th-75th percentile) age at inclusion was 62 (55-70) years and 2967 (72.0%) were men. According to the most recent diagnostic criteria, 1603 (38.9%) had DM, of which the vast majority (97.4%) was classified with type 2 (n=1566). However, only a subset was prescribed antidiabetic medications (Table 1). All together, 1078 (25.9%) of patients were current smokers, 1935 (46.9%) had hypertension, and 1644 (40.4%) reported a prior AMI. Compared with the total population, median age and body mass index were higher in patients with DM, as were the prevalence of hypertension at inclusion and the incidence of AMI during follow-up (Table 1). Kynurenines and Baseline CharacteristicsMedian values of all kynurenines were lower in women than in men (P<0.001). KA, HK, and AA were associated positively with age (ρ≥0.19; P<0.001), and except ...

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Kynurenine pathway – a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients

Cited by 82 publications

References 37 publications

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population

Metabolites associate with kidney function decline and incident chronic kidney disease in the general population

Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects

Associations of Plasma Kynurenines With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris

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