Circulating Levels of Adhesion Molecules in Chronic Kidney Disease Correlate with the Stage of Renal Disease and with C-Reactive Protein

doi:10.1016/j.arcmed.2007.01.013

Archives of Medical Research

Volume 38, Issue 5, July 2007, Pages 534-538

https://doi.org/10.1016/j.arcmed.2007.01.013 Get rights and content

Background

Patients with chronic renal failure (CRF) suffer from a series of complications linked to the atherosclerotic process in which the endothelial dysfunction mediated by the activation of some adhesion molecules plays an important role. This study aims to evaluate circulating levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) in patients with predialysis CRF, on maintenance hemodialysis (HD) and after kidney transplantation (KTx) and to correlate them with some inflammation and nutritional indexes.

Methods

Thirty two patients with predialysis CRF, 30 on maintenance HD, 36 after KTx and 28 subjects as a control group (C) were included in this study. Circulating levels of ICAM-1 and VCAM-1 were assayed using a specific sandwich ELISA kit. As inflammation indexes, TNFα and C-reactive protein (CRP) and, as nutritional indexes, body mass index (BMI), serum albumin, cholesterol, triglycerides, and fibrinogen (F) were evaluated.

Results

Serum levels of ICAM-1 and VCAM-1 were progressively higher from C to KTx patients, to those with CRF and those on HD (ANOVA for both; p <0.001). TNFα values were lower in HD subjects than in CRF patients, even if in both groups TNFα levels were greater than in Tx and control subjects. F and CRP were higher in CRF and HD vs. Tx and control subjects (ANOVA for both p <0.001). No significant correlations were observed between soluble adhesion molecules, albumin and cholesterol, whereas significant correlations were found between CRP and ICAM-1 (r = 0.41; p <0.01), CRP and VCAM-1 (r = 0.39; p <0.01) and between CRP and TNFα (r = 0.42; p <0.01). These correlations remained statistically significant even after adjustment for age and blood pressure (all p <0.01). BMI did not differ in the three patient groups.

Conclusions

Circulating levels of adhesion molecules in our study correlated positively with the stage of disease and with one of the inflammatory indexes (CRP), but not with nutritional indexes such as BMI, cholesterol and albumin. The clinical significance of our findings warrants further investigation.

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.

Section snippets

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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The role of decoy receptor 3 in inflammation and atherosclerosis in patients with chronic kidney disease and renal transplant patients
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The cardiovascular risk has been increased in chronic kidney disease associated with chronic inflammation and atherosclerosis. Decoy receptor 3, is a member of the TNF receptor superfamily and associated with inflammation and atherosclerosis. The aim of our study is to determine the relationship, between serum DcR3 levels and inflammatory markers in patients with renal transplantation, those receiving dialysis treatment and cases with chronic renal failure that did not receive replacement therapy, and to evaluate their correlation with USG findings.
A total of 150 patients aged between 22–86 years, consisting of 4 groups, namely renal transplantation, dialysis, predialysis chronic kidney disease and control groups, were included in the study. Serum decoy receptor 3, VCAM-1, ICAM-1 and IL-8 measured with ELISA method. Carotid intima-media thickness and presence of carotis arter plaque performed by ultrasound probe, non-invasively.
All serum markers were higher in dialysis and pre-dialysis chronic kidney disease groups compared to renal transplant and control groups (p < 0.05). Serum decoy receptor 3 level (median(min–max)) of renal transplant group (0.49 ng/mL (0.19–1.65)) was higher than control group (0.35 ng/mL (0.19–2.22)). There was no difference between patients receiving dialysis (0.89 ng/mL (0.41–4.98)) and patients with pre-dialysis chronic kidney disease (0.71 ng/mL (0.29–1.68)). There was no difference between patient groups in terms of the presence of plaque.
Although renal transplantation provides a significant improvement in the inflammatory process, not return completely. Inflammatory process associated with uremic milieu may predispose to atherosclerosis in patients with pre-dialysis chronic kidney disease and hemodialysis patients.
El riesgo cardiovascular se ha incrementado en la enfermedad renal crónica asociada con la inflamación crónica y la ateroesclerosis. El decoy receptor 3 (DcR3) es un miembro de la superfamilia de receptores de TNF y está asociado con inflamación y ateroesclerosis. El objetivo de nuestro estudio es determinar la relación entre los niveles séricos de DcR3 y los marcadores inflamatorios en pacientes con trasplante renal, los que reciben tratamiento de diálisis y los casos con insuficiencia renal crónica que no recibieron terapia sustitutiva, y evaluar su correlación con los hallazgos de la ultrasonografía (USG).
Se incluyeron en el estudio un total de 150 pacientes con edades comprendidas entre los 22 y los 86 años. Así, hay 4 grupos, que en concreto son: trasplante renal, diálisis, enfermedad renal crónica prediálisis y grupos de control. Suero DcR3, VCAM-1, ICAM-1 e IL-8 fueron medidos con el método ELISA. Espesor de la íntima-media carotídea y presencia de placa de la arteria carótida fue realizada por sonda ecográfica de forma no invasiva.
Todos los marcadores séricos fueron más altos en diálisis y enfermedad renal crónica previa a la diálisis grupos en comparación con los grupos de control y de trasplante renal (p < 0,05). Nivel de DcR3 en suero (mediana [min-máx]) del grupo de trasplante renal (0,49 ng/ml [0,19-1,65]) fue mayor que el grupo de control (0,35 ng/ml [0,19-2,22]). No hubo diferencia entre los pacientes que recibieron diálisis (0,89 ng/ml [0,41-4,98]) y los pacientes con enfermedad renal crónica prediálisis (0,71 ng/ml [0,29-1,68]). No hubo diferencia entre los grupos de pacientes en cuanto a la presencia de placa.
Aunque el trasplante renal aporta una mejora significativa en el proceso inflamatorio, no vuelve a su estado normal por completo. El proceso inflamatorio asociado con el medio urémico puede predisponer a la ateroesclerosis en pacientes con enfermedad renal crónica previa a la diálisis y pacientes en hemodiálisis.
Kidney transcriptome analysis of rats (Rattus norvegicus) revealed induction of renal injury and damage markers in response to melamine
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It is possible, therefore, that there may be changes in the release of adhesion molecules that facilitate these processes when thrombosis occurs. Increased levels of soluble adhesion molecules have previously been reported in HD patients [20–23] but the significance of circulating soluble adhesion molecules as predictors of native AV fistula thrombosis remains largely unknown. Adhesion of leukocytes to the vascular endothelium is one of the most important key events in the development of atherosclerosis.
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Original articleClinicalCirculating Levels of Adhesion Molecules in Chronic Kidney Disease Correlate with the Stage of Renal Disease and with C-Reactive Protein

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients and Methods

Results

Discussion

Am J Kidney Dis

Kidney Int

Am J Pathol

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int Suppl

Kidney Int

Am J Kidney Dis

Impaired endothelium-dependent vasodilation in uremia

Nephrol Dial Transpl

Vascular adhesion protein-1 (VAP-1) mediates lymphocyte-endothelial interactions in chronic kidney rejection

Eur J Immunol

Original article
Clinical
Circulating Levels of Adhesion Molecules in Chronic Kidney Disease Correlate with the Stage of Renal Disease and with C-Reactive Protein