Title |
Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study
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Published in |
BMC Nephrology, November 2016
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DOI | 10.1186/s12882-016-0387-3 |
Pubmed ID | |
Authors |
Naama Karu, Charlotte McKercher, David S. Nichols, Noel Davies, Robert A. Shellie, Emily F. Hilder, Matthew D. Jose |
Abstract |
Adults with chronic kidney disease (CKD) exhibit alterations in tryptophan metabolism, mainly via the kynurenine pathway, due to higher enzymatic activity induced mainly by inflammation. Indoles produced by gut-microflora are another group of tryptophan metabolites related to inflammation and conditions accompanying CKD. Disruptions in tryptophan metabolism have been associated with various neurological and psychological disorders. A high proportion of CKD patients self-report symptoms of depression and/or anxiety and decline in cognitive functioning. This pilot study examines tryptophan metabolism in CKD and explores associations with psychological and cognitive functioning. Twenty-seven adults with CKD were part of 49 patients recruited to participate in a prospective pilot study, initially with an eGFR of 15-29 mL/min/1.73 m(2). Only participants with viable blood samples and complete psychological/cognitive data at a 2-year follow-up were included in the reported cross-sectional study. Serum samples were analysed by Liquid Chromatography coupled to Mass Spectrometry, for tryptophan, ten of its metabolites, the inflammation marker neopterin and the hypothalamic-pituitary-adrenal (HPA) axis marker cortisol. The tryptophan breakdown index (kynurenine / tryptophan) correlated with neopterin (Pearson R = 0.51 P = 0.006) but not with cortisol. Neopterin levels also correlated with indoxyl sulfate (R = 0.68, P < 0.0001) and 5 metabolites of tryptophan (R range 0.5-0.7, all P ≤ 0.01), which were all negatively related to eGFR (P < 0.05). Higher levels of kynurenic acid were associated with lower cognitive functioning (Spearman R = -0.39, P < 0.05), while indole-3 acetic acid (IAA) was correlated with anxiety and depression (R = 0.52 and P = 0.005, R = 0.39 and P < 0.05, respectively). The results of this preliminary study suggest the involvement of inflammation in tryptophan breakdown via the kynurenine pathway, yet without sparing tryptophan metabolism through the 5-HT (serotonin) pathway in CKD patients. The multiple moderate associations between indole-3 acetic acid and psychological measures were a novel finding. The presented pilot data necessitate further exploration of these associations within a large prospective cohort to assess the broader significance of these findings. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 134 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 21 | 16% |
Student > Bachelor | 20 | 15% |
Researcher | 18 | 13% |
Student > Ph. D. Student | 18 | 13% |
Other | 7 | 5% |
Other | 15 | 11% |
Unknown | 35 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 20 | 15% |
Biochemistry, Genetics and Molecular Biology | 13 | 10% |
Agricultural and Biological Sciences | 11 | 8% |
Psychology | 10 | 7% |
Neuroscience | 8 | 6% |
Other | 27 | 20% |
Unknown | 45 | 34% |