Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in haemodialysis patients

Background: Increased levels of soluble adhesion molecules have been reported in haemodialysis (HD) patients. Recent studies have shown that recombinant human erythropoietin (rHuEPO) elicits proliferation and migration of endothelial cells and modifies endothelial function. The present study was design to explore the effects of rHuEPO on serum levels of soluble adhesion molecules in HD patients. Methods: Soluble serum levels of E‐selectin (sE‐selectin), intracellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) were measured by ELISA in 29 rHuEPO naïve HD patients (20 males, 9 females) and 10 control subjects at baseline and second month. The HD patients with a haemoglobin level lower than 10.0 mg/dL (n = 19) were administered rHuEPO therapy and other HD patients (n = 10) were followed as a placebo group. Results: Serum levels of soluble adhesion molecules were significantly higher in HD patients compared with the control group. A significant rise from the baseline in sE‐selectin levels (77 ± 70 vs 100 ± 86 ng/mL, P < 0.05) was observed 2 months after rHuEPO initiation, while sICAM‐1 and sVCAM‐1 levels decreased (271 ± 261 vs 197 ± 89 and 1043 ± 243 vs 990 ± 236 ng/mL, respectively, P < 0.05). Conclusions: The present data indicate that rHuEPO could have an important action on serum levels of soluble adhesion molecules in HD patients. rHuEPO might modify the expression of adhesion molecules from endothelial cells either. However, the exact mechanism responsible for the serum elevation of these molecules in HD patients is yet to be fully elucidated.     

Nutritional vitamin D supplementation in haemodialysis: A potential vascular benefit?

Aim: Vitamin D deficiency is highly prevalent in end‐stage renal disease and has been associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy. Although activated vitamin D has shown to be cardioprotective, the cardiovascular benefits of nutritional vitamin D (i.e. ergocalciferol or cholecalciferol) have not been explored in the dialysis population. The aim of this investigation was to evaluate the effect of ergocalciferol therapy on vascular adhesion molecules, markers of inflammation and atherosclerosis among haemodialysis patients. Methods: This was a pilot study of matched haemodialysis patients. For every patient enrolled taking ergocalciferol, an age and race matched control was recruited. Predialysis blood samples were collected and assayed for adhesion molecules (soluble vascular cell adhesion molecule‐1 (sVCAM‐1), soluble intercellular adhesion molecule‐1 (sICAM‐1), E‐selectin and P‐selectin), inflammatory cytokines (interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α)), oxLDL‐β₂GPI and IgG anticardiolipin. Results: A total of 40 haemodialysis patients were studied (20 on ergocalciferol therapy, 20 not receiving ergocalciferol therapy). Patients taking ergocalciferol had higher 25‐hydroxyvitamin D levels compared with those not taking ergocalciferol. Even though doxercalciferol usage and dosing was similar between groups, plasma sVCAM‐1, sICAM‐1 and P‐selectin concentrations were lower among ergocalciferol treated patients. No significant differences in E‐selectin, IL‐6, TNF‐α, oxLDL‐β₂GPI or anticardiolipin antibody levels were observed. Conclusion: Patients receiving ergocalciferol had lower plasma levels of vascular adhesion molecules despite equivalent use of activated vitamin D therapy. Future investigations should confirm the role of nutritional vitamin D therapy, in addition to activated D therapy, in haemodialysis patients and the potential vascular benefits of these agents.     

ICAM-1和VCAM-1测定在肾移植急性排斥反应中的临床意义

目的探讨血清可溶性细胞间粘附分子１（ｓＩＣＡＭ１）和可溶性血管细胞粘附分子１（ｓＶＣＡＭ１）在肾移植急性排斥反应中的临床意义。方法采用酶联免疫吸附法（ＥＬＩＳＡ）动态监测５６例肾移植患者术后ｓＩＣＡＭ１和ｓＶＣＡＭ１水平的变化。结果肾移植患者术后ｓＩＣＡＭ１和ｓＶＣＡＭ１水平呈规律性变化,急性排斥反应组ｓＩＣＡＭ１为（３９０．６±９１．０）ｎｇ／ｍｌ,ｓＶＣＡＭ１为（１９５７．１±４０３．１）ｎｇ／ｍｌ,明显高于移植肾功能稳定组的（１３７．３±１６．８）ｎｇ／ｍｌ、（１１１８．４±２１０．４）ｎｇ／ｍｌ和ＣｓＡ肾中毒组的（１３２．７±２４．８）ｎｇ／ｍｌ、（１２８５．８±２７０．５）ｎｇ／ｍｌ,差异有非常显著性（Ｐ＜０．０１）。结论ｓＩＣＡＭ１和ｓＶＣＡＭ１可以作为肾移植术后急性排斥反应的免疫学监测指标。     

创伤后多脏器功能衰竭患者白细胞流变性和细胞粘附分子水平的变化

目的 探讨创作后多器官功能衰竭（ＭＯＦ）患者白细胞流变性和细胞粘附分子（ＣＡＭｓ）水平的变化。方法 采用ＤＸＣ－３００Ａ型核孔膜红细胞变形能力测定仪、ＪＹＪ－Ⅲ型体外血栓血小板粘附两用仪、酶联免疫吸附法（ＥＬＩＳＡ）,分别检测了３６例创伤后ＭＯＦ患者、３１例创伤患者和３５例健康人外周血液白细胞变形能力（ＬＤ）、白细胞粘附功能（ＬＡＦ）、白细胞ＣＤ１８表达、血浆可溶性细胞间粘附分子－１（ｓＩＣＡＭ－     

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.     

Soluble Adhesion Molecules During Ex Vivo Lung Perfusion Are Associated With Posttransplant Primary Graft Dysfunction

Ex vivo lung perfusion (EVLP) enables assessment of marginal donor lungs for transplantation. We aimed to discover biomarkers in EVLP perfusate that could predict development of primary graft dysfunction (PGD). From September 2008 to August 2013, 100 clinical EVLPs were performed. Eleven patients developed PGD grade 3 within 72 h after transplant. The non‐PGD group consisted of 34 patients without PGD grade 3. Nonbilateral lung transplants or transplant after extracorporeal life support were excluded from analyses. Soluble intercellular adhesion molecule 1 (sICAM‐1), soluble VCAM‐1 (sVCAM‐1), and soluble E selectin (sE‐selectin) levels, as markers of endothelial activation, were measured in the perfusate of EVLP by enzyme‐linked immunosorbent assay and were correlated with clinical outcome. Levels of sICAM‐1 at 1 h and sVCAM‐1 at 1 and 4 h were significantly higher in the PGD group compared with the non‐PGD group. The sE selectin levels were not statistically different between the study groups. Higher levels of sVCAM‐1 at 1 and 4 h were statistically significantly associated with PGD either alone or after adjustment for other PGD risk factors. These adhesion molecules may help identify donor lungs at higher risk of PGD during EVLP.     

肾移植后尿中可溶性细胞间粘附分子-1浓度监测的临床意义

目的：评价肾移植后患者尿中可溶性细胞间粘附分子－１（ｓＩＣＡＭ－１）浓度变化的临床意义。方法：动态检测２０例肾移植患者术后２个月内尿中ｓＩＣＡＭ－１浓度的变化。结果：急性排斥反应（ＡＲ）时,ｓＩＣＡＭ－１的升高较临床诊断提早数天,并且显著高于环孢素Ａ肾中毒组;对甲基氢化泼尼松敏感的排斥反应,抗排斥治疗数天后ｓＩＣＡＭ－１下降到排斥前水平。结论：肾移植术后动态监测受者尿中ｓＩＣＡＭ－１浓度有助于ＡＲ     

An active role for soluble and membrane intercellular adhesion molecule-1 in osteoclast activity in vitro

In osteoclastogenesis, the intercellular adhesion molecule (ICAM)-1 provides a high-affinity adhesion between the osteoblast and the osteoclast precursor, thereby facilitating the interaction between receptor activator nuclear factor κB ligand (RANKL) and its receptor RANK. However, the role of soluble ICAM (sICAM) in that process remains obscure. Therefore, the purpose of this study was to determine whether sICAM and ICAM-1 play an active role in the formation and maturation of osteoclasts. Monocytes isolated from healthy donors and cultured alone or with human osteoblast were stimulated with macrophage colony-stimulating factor, sRANKL, ICAM-1 monoclonal antibody (mAb), leucocyte function antigen (LFA)-1 mAb, and/or sICAM to produce mature osteoclasts. Release of TRAP 5b and resorption area were analyzed as markers of osteoclast formation and function, respectively. The effect of ICAM-1 and sICAM stimulation on apoptosis, cathepsin K, αvβ3, collagen-1, and on RANKL/osteoprotegerin (OPG)/RANK expression was evaluated. sICAM did not modify the release of TRAP 5b from osteoclast precursors in both mono and co-culture, but induced a significant increase in resorption area in both culture systems, as well as a positive effect on cathepsin K and αvβ3 protein expression. Cross-linking ICAM-1 on osteoblast resulted in increased RANKL mRNA and caspase-3 protein expression, decreased collagen-1 mRNA expression, and decreased osteoblast survival. Stimulation of preosteoclast with sICAM produced a significant increase in preosteoclast survival and a decrease in caspase-3 expression. These results indicate that ICAM-1 and sICAM have a dual effect on bone homeostasis, increasing osteoclast activity while lowering osteoblast anabolic activity.     

Association of mineral metabolism with an increase in cellular adhesion molecules: another link to cardiovascular risk in maintenance haemodialysis?

BACKGROUND: Abnormal mineral metabolism is associated with increased cardiovascular morbidity and mortality. The exact pathogenesis linking mineral metabolism to cardiovascular risk is unknown. This study was undertaken to investigate the association between serum phosphate and/or Ca x PO(4) product with serum levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 and the degree of carotid artery atherosclerosis in patients on haemodialysis. METHODS: Seventy-three patients (46 male, 27 female; mean age 48+/-13 years, on haemodialysis for 82+/-80 months) were included in the study. All patients were stable, had no evidence of vascular disease and/or active infection. Consecutive 6 months clinical and laboratory data were obtained for each patient from their medical records and mean values were used for analysis. Serum levels of soluble adhesion molecules were assayed by ELISA. All subjects underwent a detailed evaluation of the carotid arteries. RESULTS: The percentage of patients who met all three targets of NKF-K/DOQI for phosphate, calcium and Ca x PO(4) product was 27.1%, whereas those who did not achieve the target in one, two or three parameters was 28.1, 17.7 and 14.6%, respectively. The sICAM-1 levels were significantly higher in patients who had hyperphosphataemia (serum phosphate >5.5 mg/dl; P = 0.044) and hypercalcaemia (serum calcium >9.5 mg/dl; P = 0.014), both sE-selectin and sICAM-1 levels were significantly higher in patients with Ca x PO(4) product levels above 55 mg(2)/dl(2) (P = 0.002 and P = 0.000, respectively). Soluble E-selectin and sICAM levels demonstrated a near-linear increase in parallel to the degree of deviation from mineral metabolism targets. Soluble E-selectin and sICAM levels were correlated with serum phosphate and Ca x PO(4) product, but there were no correlations between adhesion molecules and carotid measurements. CONCLUSION: These findings suggest that in stable haemodialysis patients abnormal bone mineral metabolism was associated with increased soluble adhesion molecules. These alterations in adhesion molecules may favour the development of cardiovascular changes and contribute to high cardiovascular morbidity and mortality in patients with abnormal mineral metabolism.     

Circulating levels of soluble adhesion molecules in patients with ANCA-associated vasculitis

BACKGROUND: During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules, which facilitate the binding of circulating leukocytes and their extravasation in surrounding tissue (i.e. renal tissue). The serum concentration of circulating soluble adhesion molecules is supposed to reflect the degree of this activation. OBJECTIVE: In the first part of the study, we determined if the serum levels of the soluble intercellular adhesion molecule (sICAM)-1 and the soluble endothelial cell-leukocyte adhesion molecule (sELAM)-1, in patients affected by microscopic polyangiitis (MPA), associated with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibodies (ANCA), were related to the active and the inactive vasculitis phase. In the second part of the study, we examined the changes in circulating sICAM-1 and sELAM-1 levels and the clinical outcome of renal function in these patients. METHODS: We examined 20 MPO-ANCA-positive MPA patients in an acute phase and in a remission phase, after 6 months of treatment, and 50 subjects as controls, 30 with autosomal dominant polycystic kidney disease (ADPKD) in stable chronic renal failure (CRF) and 20 healthy volunteers (HS) with normal renal function. RESULTS: Regarding serum creatinine (Cr) concentration, no significant differences were found comparing active and inactive phases in the MPA group and the CRF group. Mean serum adhesion molecule levels in the MPA group were higher in the active phase compared to the inactive phase and to the CRF and HS groups. In addition, considering the outcome of serum Cr concentrations in the MPA group, the serum adhesion molecule levels were higher and decreased more slowly in patients with final high serum Cr concentrations than in patients with final normal serum Cr concentrations. CONCLUSION: Our data suggest that in MPO-ANCA-positive MPA patients, higher sICAM-1 and sELAM-1 levels during the active phase and their slower decline during the treatment period, could be a prognostic risk factor for CRF development.     

Carotid atherosclerosis is associated with inflammation and endothelial cell adhesion molecules in chronic haemodialysis patients.

BACKGROUND: Recently emerging evidence suggests that endothelial adhesion molecules may participate in atherogenesis. The aim of the present report was to investigate the probable association of circulating ICAM-1, VCAM-1 and E-selectin with atherosclerotic disease in chronic haemodialysis (HD) patients. METHODS: One hundred and twelve HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. In addition, in a follow-up study, the survival of 81 patients after a mean period of 26 months was analysed in relation to ICAM-1 and VCAM-1 levels. RESULTS: IMT and plaque score were significantly higher in HD patients compared with control subjects (P < 0.001 and P < 0.0001, respectively). The above ultrasonographic indices were correlated with age both in controls (P = 0.0001 and P = 0.002, respectively) and HD patients (P = 0.0001 and P = 0.0001, respectively). A significant relationship was observed between IMT and systolic blood pressure (BP) both in controls and in HD patients (P = 0.002 and P = 0.01, respectively). In HD patients, plaque score was also correlated with systolic BP (P = 0.02). In HD patients, IMT and plaque score were correlated significantly with log CRP values (P = 0.01 and P = 0.01, respectively). Multivariate analysis showed that log CRP values were a strong independent contributor to plaque score (P = 0.01). IMT was significantly correlated with ICAM-1 and VCAM-1 concentrations (P = 0.0001 and P = 0.003, respectively). Multivariate analysis showed that ICAM-1 concentrations were a strong independent correlate of IMT (P = 0.001). E-selectin concentrations did not show any relation with IMT or plaque score. During the follow-up period, 13 of the 81 patients died. Survival analyses showed that patients with increased ICAM-1 had a shorter survival than patients with normal ICAM-1 values and that serum ICAM-1 levels were a strong predictor of death. CONCLUSIONS: In HD patients, carotid atherosclerosis is associated with inflammation and circulating levels of soluble adhesion molecules ICAM-1 and VCAM-1. The correlations between serum ICAM-1 and IMT and ICAM-1 and survival may indicate that this molecule could be a marker of a process that contributes to the high mortality of HD patients.     

Increased levels of soluble TNF-alpha receptors and cellular adhesion molecules in patients undergoing bioincompatible hemodialysis

BACKGROUND: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. METHODS: The serum concentrations were determined with standard ELISA assays. RESULTS: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 +/- 6.2 and 27.1 +/- 5.6 ng/ml) and HD patients (45.6 +/- 18.4 and 28.7 +/- 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 +/- 18.4 and 28.5 +/- 7.3 ng/ml) and after (HD 240) the HD session (52.1 +/- 17.4 and 30.9 +/- 8.2 ng/ml) in comparison to control values (5.6 +/- 1.3 and 2.4 +/- 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-alpha levels if (HD 0) 22.7 +/- 21.5 ng/ml and (HD 240) 21.1 +/- 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 +/- 761.8 and 567.3 +/- 218.8 ng/ml, during HD (T20): 2,172.7 +/- 759.2 and 602.3 +/- 379.9 ng/ml, and after HD (T240): 2,401.6 +/- 756.4 and 648.3 +/- 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 +/- 472.9 and 165.6 +/- 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 +/- 241.5 and 217.6 +/- 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 +/- 21.3 vs. 42.1 +/- 18.9 ng/ml and 187.9 +/- 66.9 vs. 198.8 +/- 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 +/- 54.6 and 453.2 +/- 231.1 ng/ml in patients prior to HD, 118.7 +/- 66.2 and 350.8 +/- 114.8 ng/ml during the HD session and then 132.3 +/- 61.1 and 368.3 +/- 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). CONCLUSIONS: The increased circulating TNF-alpha receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.     

Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis patients: association with malnutrition, inflammation, and cardiovascular disease.

BACKGROUND: Atherosclerotic cardiovascular disease, malnutrition, and increased levels of pro-inflammatory cytokines are common features in patients with chronic renal failure, and contribute to the high mortality rate observed in these patients. A diverse group of soluble cellular adhesion molecules (CAM) (sVCAM-1, sICAM-1 and sE-selectin) are expressed on the surface of vascular endothelial cells in response to pro-inflammatory cytokines and may play an important role in the atherogenic process. METHODS: Serum levels of sVCAM-1, sICAM-1 (n=87) and sE-selectin (n=71) were analysed in a cohort of 88 patients (50+/-1 years) with chronic renal failure. The presence of malnutrition (subjective global assessment (SGA) and serum albumin), inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), and serum hyaluronan), and cardiovascular disease (CVD) were assessed at a time-point close to the start of dialysis treatment (GFR 7+/-1 ml/min). Blood lipid parameters were also assessed. RESULTS: Significant correlations were observed between Log high-sensitivity CRP (hsCRP) and sVCAM-1 (R=0.39; P<0.01) and sICAM-1 (R=0.47; P:<0.001) levels but not between Log hsCRP and sE-selectin levels in 60 patients examined with a hsCRP assay. Also serum concentrations of Log hyaluronan correlated significantly to sVCAM-1 (R=0.34; P<0.01) and sICAM-1 (R=0.29; P<0.05) levels. Malnourished patients (SGA>1) had elevated serum concentrations of sVCAM-1 (1436+/-94 vs. 1105+/-53 ng/ml; P<0.01) compared to well-nourished patients (SGA 1). Patients with clinical signs of CVD (n=26) had elevated serum levels of sICAM-1 (282+/-18 vs. 242+/-9 ng/ml; P<0.05) compared to 61 patients without signs of CVD. Plasma Log lipoprotein (a) (Lp(a)) levels correlated significantly with sVCAM-1 (R=0.30; P<0.01). Survival analysis by the Cox regression model showed that elevated sICAM-1 was, independent of age, SGA, CVD, and Log CRP, significantly related to an increased mortality rate. CONCLUSIONS: Elevated serum concentrations of soluble adhesion molecules are found in pre-dialysis patients who are malnourished, inflamed, and have signs of cardiovascular disease. These data also suggest that sICAM-1 is an independent predictor of mortality in pre-dialysis patients. Further studies are needed to determine if inflammation causes accelerated atherogenesis via effects on soluble adhesion molecules or if elevated serum levels of soluble adhesion molecules are merely markers of endothelial activation in patients with chronic renal failure.     

The association between soluble intercellular adhesion molecule-1 levels in drained dialysate and peritoneal injury in peritoneal dialysis

Background: Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear.

Methods: We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples.

Results: Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r?=?.51, p?r?=??.44, p?r?=?.86, p?Conclusions: Intercellular adhesion molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.     

Effect of upper- and lower-limb exercise training on circulating soluble adhesion molecules, hs-CRP and stress proteins in patients with intermittent claudication.

OBJECTIVES: To investigate the effects of exercise training on levels of circulating biomarkers associated with the progression of atherosclerosis and risk of cardiovascular events in patients with intermittent claudication. METHODS: Circulating levels of soluble adhesion molecules (sVCAM-1, sICAM-1, sE-selectin), high sensitivity C-reactive protein (hs-CRP) and stress proteins (Hsp60 and Hsp70) in patients randomised to a 24-week programme of arm- or leg-cranking exercise were compared with those in usual care controls. RESULTS: Arm and leg exercise similarly improved lower-limb aerobic exercise capacity (20% vs 19%, respectively; P<0.001) and maximum walking distance (30% vs 35%, respectively; P<0.001). Improvements in training limb-specific peak oxygen consumption were attenuated for patients in the highest vs lowest quartile for circulating sVCAM-1 levels at baseline (3% vs 25% respectively, P<0.001). Although circulating hs-CRP levels tended to be lower in the arm-cranking group (-1.55 [95% CI: -1.06 to -2.26]mgl(-1)), exercise training had no effect on circulating levels of soluble adhesion molecules or stress proteins. CONCLUSIONS: These findings suggest that high levels of circulating sVCAM-1 are associated with an attenuated exercise training response and that arm-cranking exercise may provide an effective stimulus for evoking systemic anti-inflammatory adaptations in patients with intermittent claudication.     

Levels of soluble adhesion molecules are elevated in the cerebrospinal fluid of children with moyamoya syndrome

OBJECTIVE: The pathogenesis of moyamoya syndrome is unknown; however, previous studies suggested an inflammatory component. Because adhesion molecules mediate inflammation during cerebral ischemia, we measured the levels of soluble isoforms of the endothelial adhesion molecules vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin in serum and cerebrospinal fluid (CSF) samples from children with moyamoya syndrome. METHODS: Serum and CSF samples were obtained from children with moyamoya syndrome (n = 20) and patients with congenital spinal deformities (n = 20). Soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin levels were measured in enzyme-linked immunoassays. The correlation between the levels of soluble adhesion molecules and the Suzuki angiographic classification was analyzed. CSF/serum albumin index values were also measured, to determine the integrity of the blood-brain barrier. RESULTS: Compared with the control group, children with moyamoya syndrome exhibited significantly elevated CSF levels of soluble vascular cell adhesion molecule Type 1, intercellular adhesion molecule Type 1, and E-selectin. The albumin index for the moyamoya group was 9, which was significantly higher than that for the control group. However, there were no differences in the serum levels of the three soluble adhesion molecules and no correlations between age, Suzuki classification, and serum and CSF levels of adhesion molecules. CONCLUSION: Our study demonstrates increased CSF levels of soluble endothelial adhesion molecules, suggesting that children with moyamoya syndrome have ongoing central nervous system inflammation, with slight impairment of the blood-brain barrier. These soluble adhesion molecules may be clinically useful as indicators of this inflammatory process and may provide some insight into this enigmatic disease process.     

Cell surface expression and serum levels of intercellular adhesion molecule-1 in renal cell carcinoma

Intercellular adhesion molecule-1 (ICAM-1) is the natural ligand of the T-lymphocyte adhesion molecule LFA-1 (lymphocyte-function-associated antigen-1). ICAM-1 is involed in target cell recognition by T-lymphocytes, LAK cells and natural killer cells. The molecule has also been detected on a variety of normal cells and on human tumors. Renal cell carcinoma (RCC) is one of the few tumors that respond to immunotherapy, but clinical results are generally disappointing. We therefore analyzed, by immunohistochemistry, the expression of ICAM-1 in pairs of normal kidneys, RCC, and RCC metastases. Moreover, serum ICAM-1 was determined in RCC patients and compared with surface expression of cell-bound ICAM-1. Strong glomerular expression of ICAM-1 was observed in all specimens of normal kidney examined. Proximal tubuli were weakly stained in the majority of specimens. Of the tumors, 80% stained positive for ICAM-1. Although ICAM-1 was detected on the majority of extrarenal tumor specimens examined, staining was generally weaker in the metastases. Patients without metastases at initial presentation more frequently expressed ICAM-1 in their primary tumors than did patients with metastases. Levels of serum ICAM-1 (sICAM-1) were significantly higher in RCC patients than in controls with non-malignant renal diseases. Patients with an unfavorable prognosis, e.g. with advanced tumor stage or metastasis at initial presentation, had higher levels of sICAM-1 than patients with low-grade and/or low-stage tumors. An inverse correlation was observed between expression of ICAM-1 in tumors and levels of sICAM-1. On the basis of our data we suggest that cell-bound or soluble ICAM-1 is correlated with tumor-host interaction in RCC.     

Soluble adhesion molecules in children and young adults on chronic hemodialysis

Children on chronic hemodialysis (HD) present with impaired immunity that may result from disturbances in leukocyte migration, caused by changes in expression of adhesion molecules on endothelium and immunocompetent cells. However, it is still not clear whether the type of dialyzer or a single dialysis session influences the concentrations of soluble adhesion molecules in these patients. We evaluated by ELISA serum levels of soluble (s) VCAM-1, ICAM-1, L-selectin, and P-selectin in 22 patients on cuprophane HD (CU), 8 on polysulfone HD (PS), 10 on vitamin E-modified cellulose HD (VE), and 15 controls. In all HD patients, sVCAM-1 levels were elevated compared with controls and were higher in CU than in VE. The sICAM-1 concentrations were increased in VE compared with controls, but remained unchanged in CU and PS. The sL-selectin levels were reduced in all HD patients. The mean values of sP-selectin were comparable in CU, PS, and controls. The lowest levels were observed in VE. In CU patients, sVCAM-1, sICAM-1, and sP-selectin concentrations rose after HD. A single PS session had no impact on adhesion molecules, whereas a VE session increased the level of sVCAM-1. The type of dialysis membrane may change the profile of adhesion molecule concentrations, thus influencing the immune system of a child on HD. The increase in levels of adhesion molecules in the course of a single HD session, which was pronounced in CU and VE patients, suggests poor biocompatibility of these dialyzers.     

Biomarkers of endothelial dysfunction in patients with primary focal segmental glomerulosclerosis

Aim: Endothelial dysfunction occurs in nephrotic syndrome (NS) and may constitute a link between NS and vascular complications. Focal segmental glomerulosclerosis (FSGS) is a common cause of NS. This study aimed to assess endothelial markers at different stages of FSGS and define whether they were associated with thromboembolic complications and disease activity. Methods: Forty‐four patients with nephrotic‐range proteinuria and biopsy‐proven primary FSGS were included in this study. Nine of them had concurrent thromboembolisms. Thirty‐two sex‐ and age‐ matched healthy volunteers served as controls. Endothelial markers including circulating endothelial cells (CECs), soluble thrombomodulin (sTM), von Willebrand factor (vWf), soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and sE‐selectin were assessed at the commencement of the study in all participants and were repeated at 2, 6 and 12 months of follow‐up in patients without thromboembolisms. Results: Patients with FSGS during active stage showed significantly higher levels of CECs, sTM, vWf, sVCAM‐1 and sE‐selectin when compared with controls. Moreover, patients with thromboembolisms had higher CECs and vWf than those without thromboembolisms. In patients without thromboembolisms, endothelial markers except sE‐selectin had inverse correlations with serum albumin and were positively related to cholesterol. Multiple analyses showed that cholesterol and serum albumin were independent predictors of CECs and sTM, and vWf and sVCAM‐1, respectively. At follow‐up, these markers systematically decreased as the disease went into remission, but the increase in vWf and sVCAM‐1 persisted even in patients obtaining complete remission for nearly a year. In patients with no response, levels of endothelial markers exhibited no obvious change. Conclusion: Patients with FSGS had elevated markers of endothelial dysfunction, which were largely related to the activity of the disease. Meanwhile, levels of CECs and vWf were higher in patients concurrent with thromboembolisms.     

Circulating levels of ICAM-1, VCAM-1, and MCP-1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events.

BACKGROUND: Increased levels of circulating adhesion molecules and chemokines have been reported in haemodialysis (HD) patients but the influence of the HD membranes on their secretion, as well as their pathophysiological implications, remains largely unknown. METHODS: Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) were measured by immunosorbent assay (ELISA) in 81 HD patients (45 male, mean age 57+/-13 years) and 35 normal subjects. All patients had been stabilized on renal replacement therapy for >3 months and were free of active infection. Thirty-three patients (40.7%) were routinely dialysed with modified cellulose membranes and 48 patients (59.3%) were dialysed with polysulfone membranes. Blood samples were taken directly from the arteriovenous fistula immediately before and at the end of a routine HD session. RESULTS: Pre-dialysis levels were significantly elevated in HD patients compared with controls (ICAM-1 515+/-177 vs 238+/-664 ng/ml, P<0.0001; VCAM-1 2107+/-648 vs 1012+/-115 ng/ml, P<0.0001; MCP-1 427+/-148 vs 125+/-42 pg/ml, P<0.0001). The HD session resulted in a significant increase in the levels of all three molecules measured (515+/-177 vs 679+/-187 ng/ml, P<0.0001; 2107+/-648 vs 2662+/-800 ng/ml, P<0.0001; 427+/-148 vs 567+/-153 pg/ml, P<0.0001, respectively). There was no difference in pre- or post-dialysis levels of the above molecules between patients routinely dialysed with either modified cellulose or polysulfone membranes. MCP-1 levels had a positive correlation with ICAM-1 levels (r=0.41, P<0.0005). VCAM-1 levels had a negative correlation with HDL levels (r=-0.30, P<0.01) and were significantly elevated in patients with HDL <35 mg/dl compared with patients with HDL > or = 35 mg/dl (2300+/-606 vs 1890+/-633 ng/ml, P<0.005). Log-transformed exact C-reactive protein (CRP) values were significantly correlated with ICAM-1 and VCAM-1 levels (r=0.41, P<0.005 and r=0.43, P<0.005, respectively). In addition, compared with patients with normal CRP values, patients with elevated CRP had significantly increased levels of ICAM-1 (466+/-166 vs 580+/-172 ng/ml, P<0.005). Patients with cardiovascular, cerebrovascular, or peripheral vascular diseases had significantly increased serum CRP and ICAM-1 levels compared with patients with no evidence of vascular disease (19.2+/-12.9 vs 7.9+/-11.8 mg/l, P<0.001 and 608+/-189 vs 474+/-155 ng/ml, P<0.005 respectively). CONCLUSIONS: Serum levels of ICAM-1, VCAM-1, and MCP-1 are increased in HD patients and probably result from either inadequate clearance or enhanced synthesis and release. HD session resulted in a significant increase of the above molecule levels but the exact mechanism(s) responsible for these alterations are yet to be fully elucidated. Increased levels of adhesion molecules are associated with inflammation, dyslipidaemia, and cardiovascular events. However, the potential link between these processes and its clinical significance warrants further investigation.