The relationship between blood metabolites of the tryptophan pathway and kidney function: a bidirectional Mendelian randomization analysis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 07 2020
29 07 2020
Historique:
received:
10
12
2019
accepted:
14
07
2020
entrez:
31
7
2020
pubmed:
31
7
2020
medline:
17
12
2020
Statut:
epublish
Résumé
Blood metabolites of the tryptophan pathway were found to be associated with kidney function and disease in observational studies. In order to evaluate causal relationship and direction, we designed a study using a bidirectional Mendelian randomization approach. The analyses were based on published summary statistics with study sizes ranging from 1,960 to 133,413. After correction for multiple testing, results provided no evidence of an effect of metabolites of the tryptophan pathway on estimated glomerular filtration rate (eGFR). Conversely, lower eGFR was related to higher levels of four metabolites: C-glycosyltryptophan (effect estimate = - 0.16, 95% confidence interval [CI] (- 0.22; - 0.1); p = 9.2e-08), kynurenine (effect estimate = - 0.18, 95% CI (- 0.25; - 0.11); p = 1.1e-06), 3-indoxyl sulfate (effect estimate = - 0.25, 95% CI (- 0.4; - 0.11); p = 6.3e-04) and indole-3-lactate (effect estimate = - 0.26, 95% CI (- 0.38; - 0.13); p = 5.4e-05). Our study supports that lower eGFR causes higher blood metabolite levels of the tryptophan pathway including kynurenine, C-glycosyltryptophan, 3-indoxyl sulfate, and indole-3-lactate. These findings aid the notion that metabolites of the tryptophan pathway are a consequence rather than a cause of reduced eGFR. Further research is needed to specifically examine relationships with respect to chronic kidney disease (CKD) progression among patients with existing CKD.
Identifiants
pubmed: 32728058
doi: 10.1038/s41598-020-69559-x
pii: 10.1038/s41598-020-69559-x
pmc: PMC7391729
doi:
Substances chimiques
Biomarkers
0
Indoles
0
Kynurenine
343-65-7
indole-3-lactic acid
5SW11R7M7M
Tryptophan
8DUH1N11BX
Indican
N187WK1Y1J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12675Références
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