Hyperfibrinolysis, uPA/suPAR System, Kynurenines, and the Prevalence of Cardiovascular Disease in Patients With Chronic Renal Failure on Conservative Treatment

Background: Disturbances of the fibrinolytic system and kynurenine (KYN) pathway of tryptophan (TRP) metabolism have been postulated as important factors in the pathogenesis of cardiovascular disease (CVD). However, no data arc yet available oil the associations between these 2 systems in relation to CVD prevalence in patients with chronic renal failure (CRF). Methods. We evaluated TRP and its metabolites, KYN, 3-hydroxykynurenine, and quinolinic acid (QA), and their relations with the parameters of the fibrinolytic system, such as tissue-type plasminogen activators and urokinase-type (uPA) plasminogen activators, plasmin-antiplasmin (PAP) complexes, plasminogen activator inhibitor-1, and Cu/Zn superoxide dismutase (Cu/Zn Sol)) levels as the marker of oxidative stress in a population of 50 patients with CRF and 20 healthy controls. In addition, the relations of these parameters to CVD prevalence in patients with CRF were also determined. Results: Compared with controls, the CRF group had significantly increased KYNs, PAP, uPA, Soluble urokinase PA receptor (SuPAR), plasminogen activator inhibitor-1 (all P < 0.0001), and tissue-type plasminogen activators (P < 0.01) concentrations. TRP levels were significantly lower (P < 0.0001), whereas Cu/Zn SOD levels did not differ significantly between patients with CRF and controls. An accelerated PAP formation was positively correlated with age, inflammatory state, creatinine, uPA/suPAR system, 3-hydroxykynurenine, QA, Cu/Zn, Sol), and CVD prevalence, whereas it was inversely associated with TRP levels and estimated glomerular filtration rate. Multivariable analysis confirmed that QA, TRP, suPAR, and Cu/Zn Sol) levels were the independent variables significantly associated with the hyperfibrinolytic state in patients with CRF. Conclusions: This cross-sectional study has demonstrated that hyperfibrinolysis was associated with uPA/suPAR system, KYNs. oxidative status, and CVD prevalence it) patients with CRF.