Tryptophan metabolism, its relation to inflammation and stress markers and association with psychological and cognitive functioning: Tasmanian Chronic Kidney Disease pilot study

BMC Nephrology

Research Article

Emily F. Hilder¹  Naama Karu²  Robert A. Shellie³  David S. Nichols⁴  Noel Davies⁴  Charlotte McKercher⁵  Matthew D. Jose⁶ 

[1] ACROSS, School of Physical Sciences, University of Tasmania, Hobart, Tasmania, Australia;Present address: Future Industries Institute, University of South Australia, GPO Box 2471, Mawson Lakes Campus, 5001, Adelaide, South Australia, Australia;ACROSS, School of Physical Sciences, University of Tasmania, Hobart, Tasmania, Australia;Present address: The Metabolomics Innovation Centre (TMIC), Department of Biological Sciences, University of Alberta, T6G 2E9, Edmonton, Alberta, Canada;ACROSS, School of Physical Sciences, University of Tasmania, Hobart, Tasmania, Australia;Present address: Trajan Scientific and Medical, 7 Argent Place, 3134, Ringwood, Victoria, Australia;Central Science Laboratory, University of Tasmania, Hobart, Tasmania, Australia;Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia;School of Medicine, University of Tasmania, Hobart, Tasmania, Australia;Renal unit, Royal Hobart Hospital, Hobart, Tasmania, Australia;

关键词: Chronic kidney disease;    Tryptophan;    Kynurenine;    Neopterin;    Cortisol;    Inflammation;    Depression;    Anxiety;    Cognition;   

DOI  :  10.1186/s12882-016-0387-3

 received in 2015-09-08, accepted in 2016-11-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAdults 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.MethodsTwenty-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.ResultsThe 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).ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s). 2016