Increased Levels Of Tissue Factor, Adhesion Molecules, Nitric Oxide and Adiponectin In End Stage Renal Disease. A Complex Interplay

End stage renal disease (ESRD) represents the fifth (final) stage of chronic kidney disease characterized by an established kidney failure (GFR <15 mL/min/1.73 m²). To further understand the pathophysiology of ESRD, this study was designed to measure the circulating levels of tissue factor (TF), adhesion molecules, such as p-selectin (P-Sel), soluble ICAM (s-ICAM), nitric oxide and adiponectin (AD).

This study included 119 ESRD patients undergoing maintenance hemodialysis in conjunction with an ongoing IRB approved protocol on the profiling of inflammatory markers in this syndrome. Citrated blood plasma samples were collected from these patients prior to the routine dialysis session. Nitric oxide levels (NO) were measured using a commercial kit from R&D systems (Minneapolis, Minnesota) and ELISA based methods for TF, P-Sel, s-ICAM and adiponectin were also purchased from R&D systems. Chromogenic and thrombin substrate method were used to measure the anti-Xa activity thrombin generation.

Tissue factor levels were found to be increased in the ESRD group (20.4±6.1pg/ml) vs the control (11.9±2.8pg/ml). The nitric oxide level was markedly higher in the ESRD group (32±17uM) vs the controls (7±3uM). The p-selectin levels were also elevated in the ESRD group (46±20ng/ml) vs the control (31±3ng/ml). The soluble ICAM levels were higher in the ESRD group (250±112ng/ml) vs the control (180±19ng/ml). Interestingly, the adiponectin levels were also increased in the ESRD group (19.2±9.3ug/ml) vs the control (11.2±4.1ug/ml). The pre-dialysis samples of the ESRD patients exhibited detectable levels of heparin.

These studies suggest that TF, NO, p-selectin and s-ICAM levels are increased in the ESRD patient. It is of interest to note that despite that a significant number of ESRD patients were diabetic; the AD levels were increased in this group. These results suggest that while ESRD represents a pro-inflammatory/hypercoagulable state, the repeated administration of heparin and other drugs may contribute to the regulation of the hemostatic process and inflammatory balance.

No relevant conflicts of interest to declare.