Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis patients: association,vith malnutrition, inflammation, and cardiovascular disease

Background. Atherosclerotic cardiovascular disease, malnutrition, and incre ased levels of pro-inflammatory cytokines are common features in patients w ith chronic renal failure, and contribute to the high mortality rate observ ed in these patients. A diverse group of soluble cellular adhesion molecule s (CAM) (sVCAM-1, sICAM-1 and sE-selectin) are expressed on the surface of vascular endothelial cells in response to proinflammatory cytokines and may play an important role in the atherogenic process. Methods. Serum levels of sVCAM-1, sICAM-1 (n = 87) and sE-seleclin (n = 71) were analysed in a cohort of gs patients (50 +/- 1 years) with chronic ren al failure. The presence of malnutrition (subjective global assessment (SGA ) and serum albumin), inflammation (C-reactive protein (CRP), tumour necros is factor-alpha (TNF-alpha, and serum hyaluronan), and cardiovascular disea se (CVD) were assessed at a time-point close to the start of dialysis treat ment (GFR 7 +/- 1 ml/min). Blood lipid parameters were also assessed. Results, Significant correlations were observed between Log high-sensitivit y CRP (hsCRP) and sVCAM-1 (R = 0.39; P < 0.01) and sICAM-1 (R = 0.47; P < 0 .001) levels but not between Log hsCRP and sE-serectin levels in 60 patient s examined with a hsCRP assay. Also serum concentrations of Log hyaluronan correlated significantly to sVCAM-1 (R = 0.34; P < 0.01) and sICAM-1 (R = 0 .29; P < 0.05) levels. Malnourished patients (SGA > 1) had elevated serum c oncentrations of sVCAEVI-1 (1436 +/- 94 vs 1105 +/- 53 ng/ml; P < 0.01) com pared to well-nourished patients (SGA 1). Patients with clinical signs of C VD (n = 26) had elevated serum levels of sICAM-1 (282 +/- 18 is vs 242 +/- 9 ng/ml; P < 0.05) compared to 61 patients without signs of CVD. Plasma Log lipoprotein (a) (Lp(a)) levels correlated significantly with sVCAM-1 (R = 0.30; P < 0.01). Survival analysis by the Cox regression model showed that elevated sICAM-1 was, independent of age, SGA, CVD, and Log CRP, significan tly related to an increased mortality rate. Conclusions. Elevated serum concentrations of soluble adhesion molecules ar e found in pre-dialysis patients who are malnourished, inflamed, and have s igns of cardiovascular disease. These data also suggest that sICAM-1 is an independent predictor of mortality in pre-dialysis patients. Further studie s are needed to determine if inflammation causes accelerated atherogenesis via effects on soluble adhesion molecules or if elevated serum levels of so luble adhesion molecules are merely markers of endothelial activation in pa tients with chronic renal failure.