Mechanism of increases in<scp>l</scp>-kynurenine and quinolinic acid in renal insufficiency

Saito, Kuniaki; Fujigaki, Suwako; Heyes, Melvyn P.; Shibata, Katsumi; Takemura, Masao; Fujii, Hidehiko; Wada, Hisayasu; Noma, Akio; Seishima, Mitsuru

doi:10.1152/ajprenal.2000.279.3.f565

Cited by 158 publications

(182 citation statements)

References 35 publications

(33 reference statements)

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“…In multivariate analysis, chronic kidney disease was found to be an important predictor for IDO and KYN elevation. This is also in line with previous studies reporting decreased TRP and increased KYN and IDO levels in chronic kidney disease [35][36][37]. Renal excretion is known to be the main route of KYN elimination [38].…”

Section: Discussionsupporting

confidence: 93%

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Meier

Ottiger

Vögeli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). Methods: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome. Results: Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a

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Section: Discussionsupporting

confidence: 93%

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Meier

Ottiger

Vögeli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…7,9,10,15 In this report, our data were in agreement with those published previously. We found that plasma KYNA/TRP ratio had the highest CR (þ103%) among all of the observed parameters for measuring renal function due to the significant up-regulation of KYNA (þ79%) and down-regulation of TRP (-9%) in CKD.…”

Section: Discussionsupporting

confidence: 92%

“…However, increased KYN was found not only in blood of CKD patients but also in urine of the experimental animals with renal insufficiency. 7 Therefore, the elevation of blood KYN may be attributable not only to the excretory impairment of kidney but also to the up-regulation of the enzymes related to the synthesis of KYN, such as IDO. 17,18 Normally, concentration of product has a positive correlation with its substrate.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidences show that blood level of TRP was decreased while KYN and KYNA were increased in patients with CKD. [6][7][8] This phenomenon has been linked to the increased activity of the enzymes catalyzing the reactions in TRP-KYN metabolism pathway, including indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52), 9 tryptophan 2,3-dioxygenase (TDO, EC 1.13.11.11) 7,10 and kynurenine aminotransferase (KAT, EC 2.6.1.7). 10 The present study measured the plasma concentrations of TRP, KYN, and KYNA by high-performance liquid chromatography (HPLC) in hypertensive patients with and without CKD.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Kynurenic Acid/Tryptophan Ratio: A Sensitive and Reliable Biomarker for the Assessment of Renal Function

Zhao

2013

Renal Failure

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Background: Decreased tryptophan (TRP) and increased kynurenine (KYN) and kynurenic acid (KYNA) in blood have been reported in patients and experimental animals with renal diseases. We investigated if these compounds could be used as new biomarkers for the assessment of renal function. Methods: Eighty hospitalized hypertensive patients (20 with chronic kidney disease (CKD), and other 60 were considered as control) were enrolled for the investigation. Plasma TRP, KYN, and KYNA were determined by high-performance liquid chromatography. Change rate (CR) was employed to evaluate the sensitivity of the parameters of renal function. Results: CR of plasma KYNA/TRP ratio (þ103%) was much higher than the CRs of blood urea nitrogen (þ44%), serum creatinine (þ56%) and estimated glomerular filtration rate (-35%). Plasma KYNA/TRP ratio was in close relationship with blood urea nitrogen (r ¼ 0.622), serum creatinine (r ¼ 0.797), urine microalbumin/24-h (r ¼ 0.518) and estimated glomerular filtration rate (r ¼ -0.662), respectively, with all p-values <0.001. Conclusions: Plasma KYNA/TRP ratio was sensitive and reliable to indicate renal function and could be used as a new biomarker to assess the risk or presence of kidney disease.

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“…The tryptophan 2,3-dioxygenase (TDO2) enzyme is a rate limiting factor in the metabolism of the neuro-immune modulator quinolinic acid [50] and this way promotes the neurodegenerative processes.…”

Section: Introductionmentioning

confidence: 99%

Increase in Alzheimer's related markers preceeds memory disturbances: Studies in vasopressin-deficient Brattleboro rat

Várga

Klausz

Domokos

et al. 2014

Brain Research Bulletin

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Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production.We compared adult (3 month) and old (12 month), normal and vasopressin-deficient Brattleboro rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box).Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), β-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR.There was no difference between the memory of adult and aged groups. The vasopressin-deficient rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them.Thus, the one year old rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation.

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Mechanism of increases inl-kynurenine and quinolinic acid in renal insufficiency

Cited by 158 publications

References 35 publications

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Plasma Kynurenic Acid/Tryptophan Ratio: A Sensitive and Reliable Biomarker for the Assessment of Renal Function

Increase in Alzheimer's related markers preceeds memory disturbances: Studies in vasopressin-deficient Brattleboro rat

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