Tryptophan and the kynurenine pathway in haemodialysis and peritoneal dialysis

Abstract

Tryptophan is an essential amino acid necessary for the synthesis of proteins, serotonin and niacin. Main causes of tryptophan depletion are malnutrition and pro-inflammatory activity. Kynurenine and quinolinic acid, metabolites of the kynurenine pathway, may accumulate in end stage renal disease (ESRD) patients on renal replacement therapy. Objective of the study is to simultaneously measure tryptophan and kynurenine pathway metabolites and to compare the levels found in haemodialysis to that of peritoneal dialysis patients. Tryptophan, kynurenine and quinolinic acid levels, in blood from 30 ESRD, i.e. 15 haemodialysis and 15 peritoneal dialysis patients, were quantified by gas chromatography – mass spectrometry. Tryptophan was significantly (p<0.05) lower for both haemodialysis (5.3 ± 5.0 μmol/L) and peritoneal dialysis (6.7 ± 3.2 μmol/L) groups than for controls (28.4 ± 4.3 μmol/L). Kynurenine was significantly (p<0.05) higher in the haemodialysis (4.7 ± 1.9 μmol/L) versus control group (2.1 ± 0.6 μmol/L). Quinolinic acid was significantly (p<0.05) higher in both the haemodialysis (4.9 ± 2.03 μmol/L) and peritoneal dialysis (2.8 ± 2.03 μmol/L) groups than in controls (0.3 ± 0.15 μmol/L). There were no differences between the patient groups other than kynurenine being significantly (p<0.05) lower in the peritoneal dialysis (2.9 ± 0.8 μmol/L) group. Patient tryptophan levels were lower than that reported by European studies. Depletion of tryptophan and accumulation of kynurenine and quinolinic acid occur in HD and PD patients. Differences in nutritional status and infection rates may contribute to greater tryptophan depletion in developing countries than in Europe and should be further investigated.