Background:

Patients with chronic kidney disease (CKD) have a substantially increased atherothrombotic risk. The final clot structure and clot lysis time has an important role in determining the risk of atherothrombotic disease. However, the predictive role of these parameters in patients with CKD needs further clarification. 

Aim: 

To investigate the role of fibrinolysis time and clot structure on cardiovascular mortality of patients with chronic kidney disease.

Methods and results:  

462 patients with CKD stage II-IV were included in the Care4HOMe study. Patients with cardiovascular death differed significantly from patients without cardiovascular mortality with respect to presence of cardiovascular disease (CVD), presence of coronary artery disease (CAD) and CKD stage (all p < 0.001).  Therefore, to assess clot characteristics in a less confounded environment, we propensity score matched patients with presence and absence of cardiovascular death. After propensity score matching a total of 56 matched patients (i.e. N=28 with CV-death; N=28 Event-free) remained whose baseline characteristics were no longer statistically different. Clot-characteristics were assessed for each matched patient by a modified ROTEM analysis of citrated plasma with the addition of 175 ng/ml of tPA. Interestingly, clot-formation time (CFT) and maximal lysis (ML) were significantly altered in patients that suffered cardiovascular death (CFT Event-free: 150±172sec; CV-death: 80±61sec p = 0.035; ML Event-free: 30±61%; CV-death: 10±81% p = 0.021). To assess the prognostic importance of both parameters we stratified CFT and ML based on the median and calculated Kaplan-Meier curves and performed a Cox-proportional hazard regression analysis. Combined assessment revealed that a ML lower than the median significantly increased the cardiovascular mortality risk (HR 3.7 95%CI 1.3 – 10.3, p = 0.009; Log-rank 0.0059) while the stratified-CFT remained insignificant (HR 0.99 95%CI 0.99 – 1.00, p = 0.28, Log-rank p = 0.79). Additional C-statistic demonstrated that the predictive value of ML with respect to cardiovascular mortality in CKD patients was comparable to established CKD mortality predictors including Cystatin-C plasma levels and Urine Albumin/Creatin Ratio (UACR) (ML 0.69, 95%CI 0.53-0.86; CystatinC 0.70, 95%CI 0.51 – 0.80; UACR 0.70, 95%CI 0.56-0.84).  

Conclusions: 

Prolonged fibrinolysis time may be an important prognostic parameter linking atherothrombotic risk to cardiovascular mortality in patients with chronic kidney disease.