Upregulation of Microparticles, Tissue Factor, Adhesion Molecules, Nitric Oxide and Adiponectin in End Stage Renal Disease

Introduction: End stage renal disease (ESRD) represents the final stage of chronic kidney disease characterized by kidney failure (GFR <15 mL/min/1.73 m²). To understand the pathophysiology of hemostatic dysregulation in ESRD, we measured the circulating levels of microparticles (MP), tissue factor (TF), adhesion molecules, such as p-selectin (P-Sel), soluble ICAM (s-ICAM), nitric oxide (NO) and adiponectin (AD).

Methods: Citrated blood plasma samples were collected from 119 ESRD patients undergoing maintenance hemodialysis to profile various thrombotic inflammatory biomarkers. 100 normal plasma samples were collected from healthy individuals and were used as controls. MP levels were measured using an annexin binding method (Hyphen Biomedical, Paris, France). NO were measured using a kit from R&D systems (Minneapolis, Minnesota) and ELISA based methods for TF, P-Sel, s-ICAM and adiponectin were obtained from R&D systems. Chromogenic substrate methods were used to measure the heparin levels and thrombin generation.

Results: MP levels were elevated in the ESRD group (28.1nm + 6.1nm vs. the control 8.9nm +1.3nm). 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). Measured variations in thrombin generation parameters were noted. Detectable levels of heparin (.05 - 0.20 U/ml) were present in the ESRD group.

Summary/Conclusions: These studies suggest that MP, 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 also 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 in these patients.