Circulating levels of ICAM‐1, VCAM‐1, and MCP‐1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events

Background. Increased levels of circulating adhesion molecules and chemokines have been reported in haemodialysis (HD) patients but the influence of the HD membranes on their secretion, as well as their pathophysiological implications, remains largely unknown. Methods. Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) were measured by immunosorbent assay (ELISA) in 81 HD patients (45 male, mean age 57"13 years) and 35 normal subjects. All patients had been stabilized on renal replacement therapy for )3 months and were free of active infection. Thirtythree patients (40.7%) were routinely dialysed with modified cellulose membranes and 48 patients (59.3%) were dialysed with polysulfone membranes. Blood samples were taken directly from the arteriovenous fistula immediately before and at the end of a routine HD session. Results. Pre-dialysis levels were significantly elevated in HD patients compared with controls (ICAM-1 515"177 vs 238"64 nguml, P-0.0001; VCAM-1 2107"648 vs 1012"115 nguml, P-0.0001; MCP-1 427"148 vs 125"42 pguml, P-0.0001). The HD session resulted in a significant increase in the levels of all three molecules measured (515"177 vs 679"187 nguml, P-0.0001; 2107"648 vs 2662" 800 nguml, P-0.0001; 427"148 vs 567"153 pguml, P-0.0001, respectively). There was no difference in pre- or post-dialysis levels of the above molecules between patients routinely dialysed with either modified cellulose or polysulfone membranes. MCP-1 levels had a positive correlation with ICAM-1 levels (rs0.41, P-0.0005). VCAM-1 levels had a negative correlation with HDL levels (rs0.30, P-0.01) and were significantly elevated in patients with HDL -35 mgudl compared with patients with HDL P35 mgudl (2300"606 vs 1890"633 nguml, P-0.005). Log-transformed exact C-reactive protein (CRP) values were significantly correlated with ICAM1 and VCAM-1 levels (rs0.41, P-0.005 and rs0.43, P-0.005, respectively). In addition, compared with patients with normal CRP values, patients with elevated CRP had significantly increased levels of ICAM-1 (466"166 vs 580"172 nguml, P-0.005). Patients with cardiovascular, cerebrovascular, or peripheral vascular diseases had significantly increased serum CRP and ICAM-1 levels compared with patients with no evidence of vascular disease (19.2" 12.9 vs 7.9"11.8 mgul, P-0.001 and 608"189 vs 474"155 nguml, P-0.005 respectively). Conclusions. Serum levels of ICAM-1, VCAM-1, and MCP-1 are increased in HD patients and probably result from either inadequate clearance or enhanced synthesis and release. HD session resulted in a significant increase of the above molecule levels but the exact mechanism(s) responsible for these alterations are yet to be fully elucidated. Increased levels of adhesion molecules are associated with inflammation, dyslipidaemia, and cardiovascular events. However, the potential link between these processes and its clinical significance warrants further investigation.