Karu, N and McKercher, C and Nichols, DS and Davies, N and Shellie, RA and Hilder, EF and Jose, MD, Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study, BMC Nephrology, 17, (1) Article 171. ISSN 1471-2369 (2016) [Refereed Article]
© The Author(s) 2016 Licensed under Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
METHODS: 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 m2. 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.
RESULTS: 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).
CONCLUSIONS: 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.
|Item Type:||Refereed Article|
|Keywords:||Chronic kidney disease, Tryptophan, Kynurenine, Neopterin, Cortisol, Inflammation, Depression, Anxiety, Cognition|
|Research Division:||Medical and Health Sciences|
|Research Group:||Clinical Sciences|
|Research Field:||Nephrology and Urology|
|Objective Group:||Public Health (excl. Specific Population Health)|
|Objective Field:||Mental Health|
|UTAS Author:||Karu, N (Dr Naama Karu)|
|UTAS Author:||McKercher, C (Dr Charlotte McKercher)|
|UTAS Author:||Nichols, DS (Dr David Nichols)|
|UTAS Author:||Davies, N (Associate Professor Noel Davies)|
|UTAS Author:||Shellie, RA (Associate Professor Robert Shellie)|
|UTAS Author:||Hilder, EF (Professor Emily Hilder)|
|UTAS Author:||Jose, MD (Professor Matthew Jose)|
|Web of Science® Times Cited:||18|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||135 View Download Statistics|
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