Activation Markers of Thrombogenesis and Endothelial Dysfunction In End-Stage Renal Disease

Over 500,000 patients currently have ESRD and it is estimated that another 200,000 will develop ESRD in the next 5 years. Hemostatic activation resulting in cardiovascular disease accounts for over 50% of the mortality seen in this patient population. Common sequelas seen in ESRD are DVT, PE, and ACS. Derangement of biochemical markers associated with these disease states have been observed in ESRD patients. In this study we profiled several markers of thrombogenesis and endothelial dysfunction to determine their levels in the ESRD population.

117 ESRD patients on maintenance dialysis for at least 3 months over the age of 18 were included in this study. Additionally, 50 age matched control samples were obtained from healthy volunteers with no known kidney function. The markers measured include C-Reactive Protein (CRP), D-Dimer (DDMER), and Thrombomodulin (TM) which were detected by biochip array using the Randox Evidence Investigator (Antrim, United Kingdom). Additionally, Plasminogen Activator Inhibitor -1 (PAI-1) and Asymmetric Dimethylarginine (ADMA) were measured using commercially available kits by Diagnostica Stago (Paris, France) and DLD Diagnostika GmbH (Hamburg, Germany), respectively.

The mean, standard deviation, and p-value for each marker is tabulated below. Additionally, the fold increase of the ESRD samples compared to control samples were calculated and included in the table below. Compared to controls, all markers measured were increased in the ESRD samples, each of which demonstrated statistically significant p-values between the two groups. TM expressed a 5.9 fold increase in ESRD compared to controls, this was the highest fold increase amongst the markers tested. CRP, DDMER, PAI-1, and ADMA were increased at 4.4, 3.0, 1.4, and 1.6 times their control counterparts, respectively.

The results in the table demonstrate that ESRD patients have a significant upregulation in markers of thrombogenesis and endothelial dysfunction. The upregulation of CRP, TM, D-DDMER, PAI-1, and ADMA is consistent with the increased thrombotic events detected in ESRD. The upregulation of the nitric oxide inhibitor ADMA points to disturbances in vascular lumen size regulation while CRP and TM suggest significant endothelial damage. Additionally, the upregulation of PAI-1 and DDimer indicates an activation of coagulation in ESRD. The combined disruption of endothelial regulation and endothelial damage along with the upregulation of thrombogenic markers helps to explain the significant prevalence of thrombosis and cardiovascular disease in ESRD. These markers should also be evaluated for their roles in kidney disease risk stratification and prognosis.

No relevant conflicts of interest to declare.