Enhanced degradation of tryptophan in patients on hemodialysis

Background: Hemodialysis patients often present with increased concentrations of tryptophan catabolites perhaps related to an enhanced activity of tryptophandegrading 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. Patients and methods: 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 diabetesmellitus 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. Results: 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. Conclusion: We conclude that tryptophan degradation is increased in dialysis patients. The association with increased neopterin concentrations indicates activated IDO.