NDT Advance Access originally published online on February 13, 2006
Nephrology Dialysis Transplantation 2006 21(6):1603-1610; doi:10.1093/ndt/gfl005
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
Soluble adhesion molecules in end-stage renal disease: a predictor of outcome
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
Correspondence and offprint requests to: Peter Stenvinkel, MD, PhD, Department of Renal Medicine, K56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Email: peter.stenvinkel{at}ki.se
Background. Inflammation is thought to contribute to initiation and aggravation of atherosclerosis through a process predominantly mediated by adhesion molecules. The aims of this study were to investigate the association between the concentrations of circulating soluble intercellular (sICAM-1) and vascular cellular (sVCAM-1) adhesion molecules and clinical outcome, and to evaluate the effect of antihypertensive drugs on sICAM-1 and sVCAM-1 concentrations in end-stage renal disease (ESRD) patients.
Methods. We prospectively investigated 310 (191 males) incident ESRD patients, 53±12 years old, shortly before the start of renal replacement therapy. Glomerular filtration rate (GFR) was 6.4 (range 0.8–16.5) ml/min/1.73 m2. Plasma sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) kits. Survival was determined from the day of examination, with a mean follow-up period of 39 (range 1–123) months.
Results. In non-adjusted analysis, high sICAM-1 and sVCAM-1 levels were associated with all-cause and cardiovascular (P<0.001) mortality. After adjusting for age, gender, diabetes mellitus, serum cholesterol, C-reactive protein (CRP), subjective global assessment and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB), the association between high sICAM-1 and mortality remained significant for all-cause (HR 1.9; CI 1.2–2.9, P = 0.004) and cardiovascular (HR 1.8; CI 1.1–3.1, P = 0.02) mortality, and a high sVCAM-1 was associated with all-cause mortality (HR 1.7; CI 1.04–2.7, P = 0.03). Furthermore, the concentration of sICAM-1, but not sVCAM-1, was lower in patients receiving ACEI/ARB (254±83 vs 275±92 ng/ml; P<0.05) or patients receiving calcium channel blockers (CCB, 251±75 vs 273±95 ng/ml; P<0.05) than in non-users.
Conclusions. In ESRD patients, sICAM-1 and sVCAM-1 are independent predictors of all cause and cardiovascular death. The use of ACEI/ARB or CCB was associated with decreased concentrations of soluble adhesion molecules.
Keywords: angiotensin-converting enzyme inhibitors; cardiovascular disease; end-stage renal disease; inflammation; mortality; soluble adhesion molecules
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