The role of tryptophan degradation in the association between inflammatory markers and depressive symptoms in chronic dialysis patients.
Background
Among chronic dialysis patients, associations have been found between inflammatory markers and depressive symptoms. In this population, no studies have examined the mechanism linking the association between inflammatory markers and depressive symptoms. We examined whether the association between inflammatory markers and depressive symptoms is mediated by tryptophan (TRP) degradation along the kynurenine (KYN) pathway.


Methods
The data are part of an observational, prospective cohort study in five urban dialysis centres in The Netherlands. Depressive symptoms were determined with the Beck Depression Inventory. Peripheral blood was collected before dialysis to measure inflammatory markers [high sensitivity C-reactive protein (HsCRP), interleukin (IL)-1β, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)], TRP, KYN and 3-hydroxykynurenine. The KYN/TRP ratio was used as a measure of TRP degradation. The association between inflammatory markers and depressive symptoms was determined using linear regression analysis and adjusted for the KYN/TRP ratio.


Results
In total, 490 chronic dialysis patients were included. HsCRP [ β = 3.8; confidence interval (CI): 1.0-6.6], IL-6 ( β = 9.1; CI: 4.0-14.1) and TNF-α ( β = 1.3; CI: 0.9-1.7) were associated with the KYN/TRP ratio. We found significant associations between HsCRP ( β = 0.8; CI: 0.3-1.3) and IL-6 ( β = 1.2; CI: 0.3-2.2) levels and depressive symptoms. However, this association was not attenuated after adjustment for the KYN/TRP ratio. Also, no significant associations were found between the KYN/TRP ratio and depressive symptoms.


Conclusion
The association between inflammatory markers and depressive symptoms in chronic dialysis patients was not mediated by TRP degradation along the KYN pathway.
['Haverkamp|Gertrud L|GL|', 'Loosman|Wim L|WL|', 'Franssen|Casper F|CF|', 'Kema|Ido P|IP|', 'van Diepen|Merel|M|', 'Dekker|Friedo W|FW|', 'Honig|Adriaan|A|', 'Siegert|Carl E|CE|']
D000328:Adult D000368:Aged D015415:Biomarkers D002097:C-Reactive Protein D003863:Depression D005260:Female D005921:Glomerulonephritis D006801:Humans D015994:Incidence D016753:Interleukin-10 D053583:Interleukin-1beta D015850:Interleukin-6 D007737:Kynurenine D008297:Male D008875:Middle Aged D011446:Prospective Studies D006435:Renal Dialysis D014364:Tryptophan D014409:Tumor Necrosis Factor-alpha
tryptophan degradation inflammatory markers depressive symptoms chronic dialysis patients