Tryptophan metabolism in chronic kidney disease is related to the inflammation marker neopterin and to neuropsychological measures

Aim: This study examines tryptophan metabolism in Chronic Kidney Disease (CKD) and its link to consequent neuropsychological symptoms. Background: Neuropsychological disorders (depression, anxiety and cognitive dysfunction) are related to disruption in tryptophan metabolism, mainly via the kynurenine pathway, induced by inflammation and hypothalamo–pituitary– adrenal (HPA) axis activity. Tryptophan metabolites (indoles) produced by gutmicroflora are also related to inflammation and other conditions accompanying CKD.

Methods: Subjects (n = 30) were initially recruited with an eGFR of 15–29 ml/ min per 1.73 m2 and were alive at the 2-year follow-up. Neuropsychological measures were undertaken at baseline and 2 years. Serum samples were analysed for inflammation, HPA activity markers, tryptophan and ten of its metabolites.

Results: The expected accumulation of uremic molecules was observed in the serum of patients once eGFR < 15, significantly higher than patients with better kidney function (P values between 0.0002 and 0.043). High correlations were found between neopterin, Indoxyl sulfate (R = 0.62, P = 0.0003), and kynurenines (R values between 0.46 and 0.68, P values <0.0001 up to 0.01), suggesting the latter involvement of inflammation in the activation of IDO (indoleamine-(2,3)-dioxygenase) leading to tryptophan breakdown into the kynurenine pathway. Kynurenic acid was related to lower cognitive function (R = −0.38, P = 0.04), while serotonin and its turnover were related to multiple subscales of anxiety and depressive symptoms (P values between 0.001 and 0.05). Indole-3 acetic acid (partly produced by gut microflora) showed the highest correlations with anxiety and depressive symptoms.

Conclusions: Alteration in tryptophan metabolism in CKD is accompanied by systemic inflammation and lower cognitive function, anxiety and depression. This novel finding raises several targets for future interventions to improve patient symptoms and outcomes.