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.     

Higher serum levels of soluble intracellular cell adhesion molecule‐1 and soluble vascular cell adhesion molecule predict peripheral artery disease in haemodialysis patients

Aim: Serum levels of soluble intracellular cell adhesion molecule‐1 (sICAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM) and monocyte chemotactic protein 1 (MCP‐1), are elevated in patients with peripheral artery disease (PAD). However, the levels of these cell adhesion molecules in patients undergoing haemodialysis (HD) are unclear. Method: A total of 112 HD patients were included and PAD was diagnosed using the ankle‐brachial index and Doppler ultrasound. Serum levels of sICAM‐1, sVCAM‐1 and MCP‐1 were assayed using enzyme linked immunosorbent assay. Results: Out of 106 HD patients, 31 (27.7%) were diagnosed with PAD. After adjusting for risk factors, higher serum levels of sVCAM‐1 and sICAM‐1 were associated with PAD in HD patients, with an odds ratio of 5.3 (95% CI 3.3–65.5) and 2.7 (95% CI 1.2–21.8) respectively. Using sVCAM‐1 and sICAM‐1 for diagnosis of PAD in HD patients, sVCAM‐1 had a sensitivity of 72.4% and specificity of 62.3% for sVCAM‐1 and sICAM‐1 had a sensitivity of 89.3% and a specificity of 40%. MCP‐1 was not associated with PAD in HD patients. In addition, the fistula of HD patients with PAD had a lower A‐V access flow. Conclusion: sVCAM‐1 and sICAM‐1 was associated with higher risk of PAD in HD patients. Moreover, HD patients with PAD had a lower blood flow and lower A‐V access flow. Our results showed that sVCAM‐1 and sICAM‐1 may be used as screening markers for PAD in HD patients.     

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.     

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.     

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。     

Increased levels of serum matrix metalloproteinase-3 in haemodialysis patients with dialysis-related amyloidosis

Background: It is recognized that matrix metalloproteinase‐3 (MMP‐3) is abundantly expressed in active rheumatoid synovium, and that serum level of MMP‐3 is a useful marker for diagnosis of rheumatoid arthritis and for evaluation of prognosis in joint destruction. Little is known about serum MMP‐3 levels in haemodialysis (HD) patients, and thus, the association between serum MMP‐3 and dialysis‐related amyloidosis (DRA) has yet to be elucidated. Methods: Serum levels of MMP‐3 were measured by enzyme immunoassay in 150 HD patients, 90 without DRA and 60 with DRA, before HD. Simple regression analysis was performed to investigate the relationship between serum level of MMP‐3 and clinical parameters, including age, HD duration, C‐reactive protein and β2 microglobulin (BMG). Results: Serum levels of MMP‐3 were significantly higher in HD patients with DRA than in HD patients without DRA (258.2 ± 118.1 vs 201.5 ± 98.4 pg/mL, P = 0.0017), and both levels were significantly higher than those of healthy subjects (45.6 ± 13.4 pg/mL, P < 0.0001). Serum MMP‐3 levels significantly correlated with serum levels of BMG (r = 0.197, P = 0.0164) and HD duration (r = 0.168, P = 0.0427). Moreover, serum MMP‐3 levels significantly correlated with serum BMG levels in HD patients without DRA (r = 0.341, P = 0.0012), but not in HD patients with DRA. Conclusion: Our results suggest that matrix metalloproteinase activity increases in HD patients, which may be associated with BMG and DRA.     

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－     

The Evaluation of Postdialysis l-Carnitine Administration and Its Effect on Weekly Requiring Doses of rHuEPO in Hemodialysis Patients

Background. In this study, our aim was to evaluate the effect of postdialysis administration of parenteral l-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. Material and Methods. The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80–120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n = 17) and Group 2, rHuEPO therapy +l-carnitine (n = 17). l-carnitine (l-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe^{+ 2}), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. Results. In group 1 (n = 17, 13 female, four male), the mean age was 38.8 ± 12.1 years, mean period time on HD therapy was 18.1 ± 14.9 months, and mean Kt/V value was 1.48 ± 0.28. In group 2 (n = 17, 13 male, four female), the mean age was 48.1 ± 15.4 years, mean period time on HD therapy was 34.4 ± 23.0 months, and mean Kt/V value was 1.29 ± 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9–10.8 g/dl, Hct: 25.3–32.5%; in group 2, Hgb: 10.2–11.8 g/dl, Hct: 30.6–35.4%, respectively (p< 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe^{+ 2} markers (p > 0.05). But unlike serum Fe^{+ 2} markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p< 0.05). Conclusions. If other factors related to anemia are excluded, the postdialysis parenteral l-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

Effect of hyperparathyroidism on response to erythropoietin in children on dialysis

The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice weekly, was studied prospectively in 17 children and adolescents with end-stage renal disease who were either transfusion dependent or had hematocrits <25%. For convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure, hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored serially. When serum ferritin was <100 ng/ml during therapy, 6 patients received iron supplementation. rHuEPO therapy eliminated frequent transfusions in all patients; 11 of 17 patients reached the target hematocrit of 30% – 33% by week 16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously reached target at week 6±1; 6 HD patients treated intravenously reached target at week 11±3; 6 additional HD patients never reached target at this dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher than those of the other patients (P <0.005); 3 of 6 later reached a hematocrit of 30% – 33% after the rHuEPO dose was increased to 120 – 130 units/kg thrice weekly. We conclude that most pediatric dialysis patients can be treated successfully with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is markedly elevated, in which case a higher dose is likely to be needed. Received May 8, 1997; received in revised form September 16, 1997; accepted September 19, 1997     

Impact of age on cardiovascular function,inflammation, and oxidative stress in experimental asphyxial cardiac arrest

Background

Advanced age is an independent predictor of poor outcome after cardiac arrest (CA). From experimental studies of regional ischemia‐reperfusion injury, advanced age is associated with larger infarct size, reduced organ function, and augmented oxidative stress. The objective of this study was to investigate the effect of age on cardiovascular function, oxidative stress, inflammation, and endothelial activation after CA representing global ischemia‐reperfusion.

Methods

Aged (26 months) and young (5 months) rats were subjected to 8 min of asphyxia induced CA, resuscitated and observed for 360 min. Left ventricular pressure‐derived cardiac function was measured at baseline and 360 min after CA. Blood samples obtained at baseline, 120 min, and 360 min after CA were analyzed for IL‐1β, IL‐6, IL‐10, TNF‐α, elastase, sE‐selectin, sL‐selectin, sI‐CAM1, hemeoxygenase‐1 (HO‐1) and protein carbonyl. Tissue samples of brain, heart, kidney, and lung were analyzed for HO‐1.

Results

Cardiac function, evaluated by dP/dt_max and dP/dt_min, was decreased after CA in both young and aged rats, with no group differences. Mean arterial pressure increased after CA in young, but not old rats. Aged rats showed significantly higher plasma levels of elastase and sE‐selectin after CA, and there was a significant different development over time between groups for IL‐6 and IL‐10. Young rats showed higher levels of HO‐1 in plasma and renal tissue after CA.

Conclusion

In a rat model of asphyxial CA, advanced age is associated with an attenuated hyperdynamic blood pressure response and increased endothelial activation.     

Nutritional status of vegetarians on maintenance haemodialysis

Aim: Vegetarian diets have long been thought of as beneficial to health. However, vegetarian diets are often low in protein, which is contradictory to the high protein diet guideline for uraemia patients. The purpose of the study was to investigate the impact of a vegetarian diet on the nutritional status of haemodialysis (HD) patients. Methods: Patients on chronic HD for over 6 months were included in the study. The normalized protein catabolic rate (nPCR) was used to reflect daily protein intake. Biochemical markers of nutrition, anthropometric parameters, subjective global assessment (SGA) and functional activity of daily living were assessed to evaluate the nutritional status of vegetarians on chronic HD. Results: Nineteen out of 318 HD patients were vegetarians. The nPCR was lower in the vegetarian group (1.20 ± 0.24 vs 1.10 ± 0.29 g/kg per day, non‐Veg vs Veg, P < 0.05). The serum albumin and prealbumin were similar in vegetarian and non‐vegetarian HD patients. The body mass index (BMI) and mid‐arm muscular circumference (MAMC) were lower in vegetarian patients (P < 0.05). The haematocrit of vegetarians can be maintained at a level similar to that of non‐vegetarian patients but erythropoietin doses needed were higher in vegetarian patients (P < 0.05). The muscle strength evaluated by the hand‐grip test, SGA and activities of daily living were similar in vegetarians and non‐vegetarians. Conclusion: The present study revealed that HD patients on vegetarian diets might have a smaller BMI, but SGA and function of daily activities were similar to those of the non‐vegetarians. The haematocrit of vegetarians can be maintained with a higher erythropoietin dose.     

Randomized clinical trial on acute effects of i.v. iron sucrose during haemodialysis

Aim: Haemodialysis induces endothelial dysfunction by oxidation and inflammation. Intravenous iron administration during haemodialysis could worsen endothelial dysfunction. The aim of this study was to ascertain if iron produces endothelial dysfunction and the possible neutralizing effect of N‐acetylcysteine when infused before iron. The oxidative and inflammatory effects of iron during haemodialysis were also assessed. Methods: Forty patients undergoing haemodialysis were studied in a randomized and cross‐over design with and without N‐acetylcysteine infused before iron sucrose (50 or 100 mg). Plasma Von Willebrand factor (vWF), soluble intercellular adhesion molecule‐1 (sICAM‐1) levels, malondialdehyde, total antioxidant capacity, CD11b/CD18 expression in monocytes, interleukin (IL)‐8 in monocytes and plasma IL‐8 were studied at baseline and during haemodialysis. Results: Haemodialysis produced significant (P < 0.001) increase in plasma vWF, sICAM‐1, malondialdehyde, IL‐8 and CD11b/CD18 expression in monocytes, as well as decrease in total antioxidant capacity. Iron induced significant increase in plasma malondialdehyde and IL‐8 in monocytes, but had no effect on total antioxidant capacity, CD11b/CD18 expression, plasma IL‐8, vWF and sICAM‐1. The addition of N‐acetylcysteine to 50 mg of iron produced a significant (P = 0.040) decrease in malondialdehyde. Conclusion: Standard (100 mg) and low (50 mg) doses of iron during haemodialysis had no effects on endothelium. Iron only had minor effects on inflammation and produced an increase in oxidative stress, which was neutralized by N‐acetylcysteine at low iron dose. Haemodialysis caused a significant increase in oxidative stress, inflammation and endothelial dysfunction markers.     

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.     

Low-level laser irradiation modifies the effect of hyperglycemia on adhesion molecule levels

Endothelium plays a key role in maintaining vascular homeostasis by secreting active factors involved in many biological processes such as hemostasis, angiogenesis, and inflammation. Hyperglycemia in diabetic patients causes dysfunction of endothelial cells. Soluble fractions of adhesion molecules like sE-selectin and vascular cell adhesion molecule (sVCAM) are considered as markers of endothelial damage. The low-level laser therapy (LLLT) effectively supports the conventional treatment of vascular complications in diabetes, for example hard-to-heal wounds in patients with diabetic foot syndrome. The aim of our study was to evaluate the effect of low-energy laser at the wavelength of 635 nm (visible light) and 830 nm (infrared) on the concentration of adhesion molecules: sE-selectin and sVCAM in the supernatant of endothelial cell culture of HUVEC line. Cells were cultured under high-glucose conditions of 30 mM/L. We have found an increase in sE-selectin and sVCAM levels in the supernatant of cells cultured under hyperglycemic conditions. This fact confirms detrimental influence of hyperglycemia on vascular endothelial cell cultures. LLLT can modulate the inflammation process. It leads to a decrease in sE-selectin and sVCAM concentration in the supernatant and an increase in the number of endothelial cells cultured under hyperglycemic conditions. The influence of LLLT is greater at the wavelength of 830 nm.     

Serum VCAM-1, ICAM-1, and L-selectin levels in children and young adults with chronic renal failure

Children and young adults with chronic renal failure (CRF) present with an impaired immune response. Our aim was to analyze whether leukocyte migration, determined by adhesion molecules, is disturbed in the course of CRF, hemodialysis (HD), and peritoneal dialysis (PD). Soluble (s) VCAM-1, ICAM-1, and L-selectin serum levels were evaluated by ELISA in 15 patients with CRF, 22 patients on cuprophane membrane HD, 24 patients on PD, and in 15 controls. The sVCAM-1 levels in all groups were significantly elevated compared with controls. The levels in HD patients were higher than in CRF patients (P <0.05), while levels in PD patients were higher than in CRF and HD (P <0.001 and P <0.01, respectively). The sICAM-1 concentrations in CRF and PD patients were significantly elevated compared with controls (P <0.001 and P <0.0001, respectively); in PD patients sICAM-1 levels were higher than in HD patients (P <0.001), but there were no differences between other groups. sL-selectin levels were decreased in all groups compared with controls. The levels in HD patients were the lowest and the differences, compared with CRF and PD patients, were significant (P <0.05 and P <0.01, respectively). Children and young adults with CRF and on maintenance dialysis have altered concentrations of soluble adhesion molecules, resulting from either inadequate clearance or disturbed synthesis and release. The differences in sVCAM-1 levels between CRF and both groups of patients on dialysis, as well as the differences in sL-selectin concentrations between HD and CRF patients, indicate that these disturbances are aggravated by maintenance dialysis, particularly HD.     

IL-10 genotype predicts serum levels of adhesion molecules, inflammation and atherosclerosis in hemodialysis patients

BACKGROUND: Hemodialysis (HD) patients suffer from inflammation and accelerated atherosclerosis that accounts for a large number of premature deaths. The anti-inflammatory interleukin (IL)-10 gene is polymorphic and potential direct effects of IL-10 gene polymorphisms on the circulating serum levels of adhesion molecules, inflammation and atherosclerosis in HD patients still have to be elucidated. METHODS: In a cross-sectional study, circulating serum levels of vascular cell adhesion molecule-1 (VCAM-1), E-selectin (E-selectin), and intracellular adhesion molecule-1 (ICAM-1), serum albumin and C-reactive protein (CRP) were measured in 121 HD patients (70 male and 51 female, with mean age 49 +/- 18 yrs). Carotid artery intima media thickness (IMT) was evaluated by Doppler ultrasonography. Patients were genotyped for the polymorphic base at position -1082 of the IL-10 promoter sequence by polymerase chain reaction (PCR). RESULTS: Circulating serum levels of all three adhesion molecules were higher in patients with -1082/AA genotype (p = 0.001). Higher serum albumin levels together with lower CRP levels were observed in patients with -1082/GG genotype (p < 0.05). Prevalence of atherosclerosis was higher in patients with -1082/AA genotype compared to heterozygous and -1082/GG genotype (41, 34 and 26%, respectively, p = 0.018). CONCLUSIONS: These results suggest that IL-10 gene polymorphism has an effect on inflammatory process and atherosclerosis in HD patients. Endothelial protective functions of IL-10 can modulate the circulating serum levels of adhesion molecules. Therefore, IL-10 gene polymorphism could lead to high or low inflammatory process and consequently, to atherosclerosis. IL-10 genotyping can define a high-risk group for atherosclerosis among HD patients.     

Efficacy of low‐dose i.v. iron therapy in haemodialysis patients

Aim: i.v. iron therapy is more effective in maintaining adequate iron status in haemodialysis (HD) patients than oral iron therapy (OIT). However, data on lower doses of i.v. iron therapy are insufficient. Methods: A non‐randomized, open‐label study was performed to compare the efficacy of low‐dose (≤50 mg/week of iron sucrose) i.v. iron therapy (LD‐IVIT) with OIT in HD patients with 100–800 µg/L serum ferritin levels over 4 months. Results: Eighty‐nine patients in the LD‐IVIT group (40 men, 49 women; aged 61 ± 13 years) and 30 patients in the oral iron therapy group (17 men, 13 women; aged 59 ± 7 years) were evaluated. After 4 months of each treatment, serum ferritin levels increased from 398 ± 137 to 529 ± 234 µg/L in the LD‐IVIT group (P < 0.01) but decreased from 351 ± 190 to 294 ± 175 µg/L in the OIT group (P < 0.01). In the LD‐IVIT group, transferrin saturation (from 28% ± 11% to 30% ± 14%, P = 0.49), weekly doses of recombinant human erythropoietin (from 5822 ± 2354 to 5636 ± 2306 IU/week, P = 0.48) and haemoglobin (from 101 ± 9 to 103 ± 9 g/L, P = 0.15) levels remained stable. Conclusion: LD‐IVIT may be one of the regimens that may be considered for maintaining iron status in HD patients. However, efficacy of LD‐IVIT should be verified by further randomized study.     

Treatment with a cyclin-dependent kinase inhibitor, seliciclib, is effective in reducing glomerular macrophage numbers and the severity of established experimental glomerulonephritis

Aim: The cyclin‐dependent kinase inhibitor, seliciclib (R‐roscovitine, CYC202), has anti‐proliferative activity through its inhibition of cyclin‐dependent kinase 2. We hypothesized that treatment with seliciclib would reduce glomerular macrophage numbers and glomerular crescent formation in experimental crescentic glomerulonephritis even when treatment is started after onset of disease. Method: Nephrotoxic nephritis (NTN) was induced in Wistar Kyoto rats. In experiment 1, seliciclib (150 mg/kg per day) was given by oral gavage from 1 h before induction of NTN and continued to day 14. In experiment 2, treatment was started on day 4 of NTN and continued to day 14 in order to examine the effect of seliciclib in established glomerulonephritis. Results: In experiment 1, seliciclib reduced proteinuria (119.5 ± 13.9 vs 191.4 ± 18.8 mg/day, P < 0.01), serum creatinine (54.0 ± 3.0 vs 81.0 ± 2.5 µmol/L, P < 0.005) and glomerular crescent score (23.9 ± 2.1 vs 44.6 ± 2.2, P < 0.005) in comparison with controls. In experiment 2, seliciclib ameliorated established glomerulonephritis, with reduction in proteinuria (58 ± 16 vs 165 ± 13 mg/day, P < 0.005), serum creatinine (39 ± 3 vs 62 ± 5 µmol/L, P < 0.05), glomerular macrophage numbers (6.8 ± 2.5 vs 18.5 ± 1.2 ED1+ cells per glomerular cross section, P < 0.05), glomerular cell proliferation (1.2 ± 0.37 vs 4.2 ± 0.80 bromodeoxyuridine (BrdU)+ cells per glomerular section, P < 0.05) and crescent score (10.8 ± 1.6 vs 43.9 ± 1.4, P < 0.05), in comparison with the controls. Conclusion: Seliciclib is effective in both prevention and treatment of established crescentic glomerulonephritis in Wistar Kyoto rats, in association with a reduction in the number of glomerular macrophages. We suggest that seliciclib, or other cyclin‐dependent kinase inhibitors, may represent a novel therapeutic approach for patients with proliferative glomerulonephritis.     

Influence of Oral Vitamin E Therapy on Micro-Inflammation and Cardiovascular Disease Markers in Chronic Hemodialysis Patients

Background. The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. Methods. 29 HD patients were randomized into two groups: 15 patients were treated orally with 400mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical – TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. Results. Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23±11.94 vs. 11.41±1.94 mIU/L, p<0.001; CRP: 5.20±3.50 vs. 3.40±3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. Conclusion. Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.     

Conventional nutritional counselling maintains nutritional status of patients on continuous ambulatory peritoneal dialysis in spite of systemic inflammation and decrease of residual renal function

Aim: To evaluate the effect of nutritional counselling on nutritional status in peritoneal dialysis patients. Methods: Twenty‐nine peritoneal dialysis patients were randomly selected to receive conventional nutritional counselling during 6 months of follow up. All patients had monthly clinical and biochemical evaluations, and assessments of dialysis adequacy, inflammation and nutritional status at 0, 3 and 6 months. Results: Moderate‐severe malnutrition decreased 28% whereas normal nutrition increased 23% at final evaluation (non‐significant). Calorie and protein intake remained stable throughout the study (baseline vs final, calorie: 24 ± 8 vs 23 ± 5 Kcal/kg; protein: 1.1 ± 0.5 vs 1.0 ± 0.3 g/Kg, respectively). On the other hand, triceps (16 ± 6 vs 18 ± 8 mm) and subscapular (17 ± 8 vs 20 ± 5 mm) skinfold thicknesses, and mid‐arm circumference (27 ± 3 vs 28 ± 3 mm) significantly increased; mid‐arm muscle area displayed a non‐significant trend to increase (30 ± 9 vs 31 ± 9 cm²) whereas serum albumin significantly increased at the end of study (2.67 ± 0.46 vs 2.94 ± 0.48 g/dL). At final evaluation, median renal creatinine clearance decreased (6.3 (0.8–15.3) vs 2.0 (0.1–6.3) L/week per 1.73 m²) whereas interleukin‐6 increased (2.33 (1.9–7.0) vs 4.02 (2.1–8.4) pg/mL). Conclusion: Even though conventional nutritional counselling, as an isolated measure, did not significantly improve all nutritional parameters, it prevented a greater deterioration during 6 months. Nutritional counselling maintained the nutritional status in spite of a decrease in residual renal function and higher systemic inflammation.