Hypercoagulability is independently associated with kynurenine pathway activation in dialysed uraemic patients

Patients with end-stage renal disease (ESRD) exhibit features of a hypercoagulable state, which may contribute to atherosclerosis. Kynurenines are the metabolites of tryptophan degradation in mammals. We examined the relationship between coagulation activation and kynurenines in 92 patients with ESRD on maintenance haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) and 20 healthy controls. We measured the plasma levels of: tissue factor (TF), its pathway inhibitor (TFPI), the marker of coagulation activation - prothrombin fragments 1+2 (F(1+2)), kynurenine (KYN) and its metabolites: kynurenic (KYNA), anthranilic (AA) and quinolinic (QA) acids. The ratio of KYNA to KYN (kyna/kyn), AA to KYN (aa/kyn) and QA to KYN (qa/kyn), reflecting intensified activity of enzymes which converted KYN to its metabolites, were also determined. Measured coagulation parameters and kynurenines were significantly elevated in ESRD patients compared to controls. TF, TFPI and F(1+2) were significantly associated with AA, aa/kyn, QA and qa/kyn ratio. Multiple regression analysis showed that fibrinogen (p<0.01) and above mentioned KYN metabolites (all p<0.05) were the independent variables significantly associated with increased F(1+2) levels, reflecting hypercoagulability in ESRD patients. In conclusion, this study represents the first to investigate both the coagulation system and KYN pathway in ESRD patients. The coagulation was enhanced in dialysed uraemic patients compared with the healthy controls demonstrated by increased TF, TFPI and F(1+2) levels. These changes were correlated with activation of the KYN pathway. Finally, fibrinogen and KYN metabolites are independently and significantly associated with the hypercoagulable state in uraemic patients on CAPD and HD treatment.