Original articleClinicalCirculating Levels of Adhesion Molecules in Chronic Kidney Disease Correlate with the Stage of Renal Disease and with C-Reactive Protein
Introduction
The clinical course of patients with chronic renal failure (CRF) is conditioned by a series of immunological and inflammatory alterations which, in turn, lead to cardiovascular diseases (1). These processes are reflected in the changing expression of the membrane-bound receptors of adhesion molecules and the altered release of endothelial factors, which are believed to play a significant role in cardiovascular morbidity and mortality (2).
Serum levels of soluble intercellular and vascular adhesion molecules (ICAM1, VCAM1) and cytokines such as tumor necrosis factor-α (TNFα) are reported to be increased in conservatively treated renal patients (3) and in kidney transplanted patients (4) with acute or chronic rejection (5). ICAM-1 has also been found to correlate with C-reactive protein (CRP) in predialysis patients (6). Stenvinkel reported that in end-stage renal disease (ESRD) patients, chronic inflammation may be associated with endothelial dysfunction (7). Increased levels of soluble adhesion molecules and cytokines have previously been reported in patients with CRF, both on conservative treatment and on hemodialysis (HD), but the influence of dialysis membranes on their secretion as well as their pathological and clinical implications remains largely unknown (8).
Protein-energy malnutrition is another condition that has been shown to be associated with increased cardiovascular mortality in CRF (1) and in HD patients (9). In fact, authors have reported low serum albumin concentrations to be associated with increased mortality risk in patients on renal replacement therapy (RRT) (10).
Investigating the role of TNFα in mediating endothelial dysfunction is of interest because markedly elevated serum levels of this cytokine have been documented in ESRD (11). The exact mechanism(s) by which various pro-inflammatory mediators, such as TNFα, cause endothelial dysfunction are not yet known; some authors have reported that pro-inflammatory mediators induce nitric oxide (NO) synthase expression in cultures of endothelial cells and a decreased expression of cytochrome P450 (12).
The aim of the present study was to investigate circulating levels of ICAM-1 and VCAM-1 in patients with predialysis CRF, on maintenance HD and after KTx and to correlate them with some indexes of inflammation and nutrition.
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Patients and Methods
Between October 2003 and February 2004, 32 patients with predialysis CRF, 30 patients undergoing HD maintenance treatment with polysulfone dialyzers three times a week, 36 patients after kidney allotransplantation (mean time after transplantation 201.7 ± 160.4 months), and 28 healthy controls entered the study. All HD patients had been on dialysis for >12 months. Non-residual renal function was evident in all HD patients. In the CRF group the disease was attributed to glomerulonephritis (16
Results
Clinical data of the four groups included in the study are reported in Table 1. HD and CRF patients were older than KTx and control subjects, and ANOVA demonstrated significant differences for all other variables except for sex and BMI. Serum fibrinogen and albumin were, respectively, higher and lower in HD patients than in the other groups.
Figure 1 shows serum levels of CRP in the four groups studied. There is a progressive increase from controls to KTx, CRF and to HD with a significant
Discussion
The binding and recruitment of circulating leukocytes to the vascular endothelium and their further migration into the subendothelial spaces are major processes in the development of atherosclerosis and are mediated through diverse families of cellular adhesion molecules, which are expressed on the surface of leukocytes and vascular endothelial cells (13). Selectin mediates the initial rolling of leukocytes along the endothelium, whereas vascular cell adhesion molecule-1 (VCAM-1) and
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