Endothelial function and novel adhesion molecule CD44 in kidney allograft recipients.

BACKGROUND

Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these 2 processes and inflammation is closely related to endothelial dysfunction.

PATIENTS AND METHODS

This cross-sectional study on serum concentrations of markers of endothelial damage and inflammation in relation to adhesion molecules was performed in 90 kidney allograft recipients and 30 healthy volunteers. We measured markers of endothelial damage-von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), CD146, CD44, and CD40L; markers of inflammation-high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6); and other hemostatic parameters-thrombin-antithrombin complexes (TAT), plasmin-antiplasmin complexes, and thrombin activatable fibrinolysis inhibitor (TAFI) using commercially available kits.

RESULTS

Markers of endothelial dysfunction and inflammation were significantly elevated in kidney allograft recipients compared with control subjects. CD44 was independently related to hsCRP (r = .37; P < .01), ICAM (r = .23; P < .05), eGFR (r = -.37; P < .01), thrombomodulin (r = .43; P < .001), VCAM (r = -.44; P < .001), hemoglobin (r = -.26; P < .01), red blood cell count (r = -.25; P < .05), creatinine (r = .37; P < .01), CD146 (r = .34; P < .01), and CD40L (r = .23; P < .05). Upon multiple regression analysis the predictors of elevated CD44 were hsCRP concentration (beta = .25; P < .05), CD146 (beta = .39; P < .05), creatinine (beta = .55; P < .01), and thrombomodulin (beta = .39; P < .05) with an adjusted R(2) = .40 (F = 4.12; P < .00028; SE of estimate = 151.19).

CONCLUSIONS

As demonstrated in multiple regression analysis, kidney function was strictly linked to the degree of inflammation and endothelial injury. Endothelial cell injury and the presence of an inflammatory state, as reflected by elevated marker concentrations, and endothelial activation/injury may play roles in the pathogenesis of atherosclerosis and cardiovascular complications among kidney allograft recipients.