Enhanced degradation of tryptophan in patients on hemodialysis

Hemodialysis patients often present with increased concentrations of tryptophan catabolites perhaps related to an enhanced activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) that is inducible by pro-inflammatory stimuli. The often chronic inflammation and immune activation status in dialysis patients may accelerate tryptophan degradation, which could influence patients' psychological performance.

In this study, plasma concentrations of kynurenine and tryptophan were determined by HPLC in 75 dialysis patients, aged 65.3 ± 15.0 years. Forty patients were female, 35 male; 21 (28%) had diabetes mellitus Type 1 or 2 and 32 (43%) suffered from sleep disturbances and/or depression. Their dialysis vintage was 4.26 ± 4.72 years. HPLC results were compared to concentrations obtained from 40 healthy blood donors, to immune activation marker neopterin, and to psychological test results based on INTERMED scores.

Compared to those in healthy controls, tryptophan concentrations were decreased in patients. Neopterin, kynurenine and the kynurenine to tryptophan ratio (kyn/trp, an index of tryptophan degradation) were increased in patients (all p < 0.01). Kyn/trp correlated with neopterin concentrations (rs = 0.393, p < 0.01). INTERMED scores were 21.0 + 8.4 and slightly higher in females (U = -1.831, p < 0.07); they correlated with tryptophan concentrations (rs = -0.227, p < 0.05) but with no other parameter studied. Data point to a possible relationship between tryptophan metabolic disturbances and psychologic presentation of patients, although only a rather weak relationship was found.

We conclude that tryptophan degradation is increased in dialysis patients. The association with increased neopterin concentrations indicates activated IDO.