Soluble adhesion molecules in end-stage renal disease: a predictor of outcome.
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 m(2). 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.
Department of Renal Medicine and Baxter Novum, K56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Mohamed E
ME
Suliman
A Rashid
AR
Qureshi
Olof
O
Heimbürger
Bengt
B
Lindholm
Peter
P
Stenvinkel
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000187:drug effects; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1