Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients

Abstract

Background: Vascular cell adhesion molecule 1 (VCAM-1) is involved in leukocyte-endothelial cell interaction and has a pivotal role in inflammation. Whether it contributes to excessive mortality in dialysis patients remains uncertain. In this study, we examined circulating soluble VCAM-1 (sVCAM-1) in relation to different clinical and biochemical parameters, as well as mortality and cardiovascular events, in peritoneal dialysis (PD) patients.

Methods: Values for serum sVCAM-1, together with C-reactive protein (CRP), homocysteine, albumin, lipid profile, blood hemoglobin, and indices of dialysis adequacy, were determined at study baseline, and echocardiography was performed in 160 long-term PD patients. Patients were followed up for a mean of 35 +/- 16 (SD) months.

Results: Serum sVCAM-1 levels were elevated in our continuous ambulatory PD (CAPD) patients and showed a negative correlation with residual glomerular filtration rate (GFR; P < 0.001) and low-density lipoprotein (LDL) cholesterol level (P = 0.004), but a positive correlation with left ventricular mass index (P = 0.025). Using Kaplan-Meier analysis, overall survival rates at 2 years were 96.2%, 75.2%, and 50.6% for patients in the lower, middle, and upper tertiles of sVCAM-1 levels, respectively (P < 0.0001). Fatal and nonfatal cardiovascular event-free survival rates were 58.2%, 56.9%, and 19.4% for patients in the lower, middle, and upper tertiles, respectively (P < 0.0001). Using Cox regression analysis with adjustment for confounding covariates, every 100-ng/mL increase in sVCAM-1 level was associated with 8% (95% confidence interval, 1.03 to 1.13) and 5% (95% confidence interval, 1.00 to 1.10) increases in risk for death and fatal and nonfatal cardiovascular events, respectively. Its significance for all-cause mortality remained with additional adjusting for LDL cholesterol level, but was lost when adjusting for residual GFR. Its association with cardiovascular events became insignificant when adjusting for LDL cholesterol level or residual GFR. Furthermore, patients with both sVCAM-1 and CRP levels elevated at the 50th percentile or greater were associated with the greatest death and fatal and nonfatal cardiovascular event rates compared with those with either CRP or sVCAM-1 level elevated at the 50th percentile or greater.

Conclusion: Circulating sVCAM-1 levels show an important link with residual renal function, LDL cholesterol level, and cardiac hypertrophy in CAPD patients. Furthermore, residual renal function, which correlates inversely with circulating sVCAM-1 level, shows an important association with all-cause mortality and cardiovascular events and displaces sVCAM-1 level from the models for all-cause mortality and future cardiovascular events in CAPD patients. Additional study is needed to explore possible mechanistic links between inflammation, soluble adhesion molecules, residual renal function, and cardiac hypertrophy in CAPD patients.