Peri-aortic fat tissue and malnutrition-inflammation-atherosclerosis/calcification syndrome in end-stage renal disease patients.

PURPOSE: Thoracic peri-aortic fat tissue (PFT) is considered as a metabolically active organ in atherosclerosis. Malnutrition, inflammation and atherosclerosis/calcification (MIAC) are the most commonly encountered risk factors of cardiovascular disease in end-stage renal disease (ESRD) patients. Calcification of the aorta was found to be an important cardiovascular risk marker predicting future events, morbidity and mortality in this population. We aimed to investigate the relationship between PFT, MIAC syndrome and thoracic aortic calcification (TAC) in ESRD patients. METHODS: Seventy-nine ESRD patients receiving hemodialysis (HD) or peritoneal dialysis (PD) and 20 control subjects were enrolled in this cross-sectional study. PFT and TAC were assessed using a 64-MDCT scanner. Patients with serum albumin <3.5 g/dL were defined as patients with malnutrition; those with serum C-reactive protein level >10 mg/L had inflammation, and those with coronary artery calcification score (CACS) >10 had atherosclerosis/calcification. RESULTS: TAC and PFT were significantly higher in ESRD patients compared with control subjects. There was a statistically significant relationship between PFT and TAC in ESRD patients (r = 0.458, p < 0.0001). PFT was found to be significantly increased when the MIAC components increased. PFT was positively associated with age, BMI, uric acid, hemoglobin and CAC. The multivariate analysis revealed that age and uric acid were independent predictors of increased PFT. Twenty-four (30.4 %) patients had none, 30 (37.9 %) had one component, 17 (21.5 %) had two components, and 8 (10.2 %) had all MIAC components. PFT was highest among patients having all three components (28.6 cm(3)) and lowest among those who do not have the MIAC syndrome (8.54 cm(3)). TAC was highest among patients having all three components (179.2 HU) and lowest among those who do not have the MIAC syndrome (0 HU). CONCLUSIONS: We found a relationship between PFT and MIAC syndrome in ESRD patients.

To study the correlation between carrier status of nasal Staphylococcus aureus in patients on haemodialysis with hepatitis C, hepatitis B and their sociodemographic features.

AIM: To study the correlation of nasal Staphylococcus aureus carrier status in patients on haemodialysis, infected by hepatitis C virus (HCV), hepatitis B virus (HBV), and their sociodemographic features. SUBJECTS AND METHODS: A survey, including patients' sociodemographic features, was applied to patients by physicians in face to face interviews. Medical records regarding their serologic data were recorded from haemodialysis centres. Nasal swab samples of 2 cm depth from both nostrils of patients were obtained for nasal culture. Samples were inoculated in 5% sheep blood agar and incubated in an incubator at a temperature of 37 degrees C for 24 hours. The results were studied by the same microbiologist. RESULTS: A total of 185 patients were enrolled in the study. According to culture results, 14.1% of patients (n = 26) had methicillin sensitive Staphylococcus aureus (MSSA) and 1.1% (n = 2) had methicillin resistant Staphylococcus aureus (MRSA). Status of viral hepatitis was 3.8% (n = 8), 10.8% (n = 20) for HBV and HCV respectively. Forty per cent (n = 8) of patients with HBV (+) had MSSA carrier status. Statistically significant positive correlation between MSSA and HCV carrier was detected (r = 0.325, p = 0.001) but not between HBV carrier and MSSA (p = 0.255). CONCLUSION: In the present study, significant positivity was detected between MSSA carrier status and HCV in patients on haemodialysis and who have lived together with < or = 2 family members at home. Particularly, statistically significant correlation between HCV(+) and MSSA carrier was observed.

A case of crescentic IgA nephropathy treated with prednisolone and cyclophosphamide.

IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, and currently is known to be an important cause of end stage renal disease (ESRD). Hypertension, proteinuria more than 1 g/d, and the presence of severe lesions on initial renal biopsy such as crescents and interstitial fibrosis are the most significant predictive factors for progression to ESRD. Despite its prevalence and clinical importance, there is no consensus for the treatment of patients with risk factors for a worse prognosis. Our aim is to describe here a case of crescentic IgAN, and to emphasize the effect of immunosuppressive treatment.

Low serum fetuin-A concentration predicts poor outcome only in the presence of inflammation in prevalent haemodialysis patients.

BACKGROUND: Fetuin-A, a negative acute phase protein that inhibits vascular calcification, has a controversial association with mortality in chronic kidney disease (CKD) patients. Chronic inflammation, which is common in CKD, may promote vascular calcification. MATERIALS AND METHODS: We investigated the impact of inflammation on the relationship between serum fetuin-A and mortality (42 months) in 222 prevalent haemodialysis (HD) patients. RESULTS: Serum fetuin correlated negatively with comorbidity score (assessed by Davies score) and circulating inflammatory markers. Patients with low fetuin-A levels (< median) had higher mortality (Hazard ratio 'HR' 2.2; CI 1.4-3.5, P < 0.001), but this association was lost after adjustment for age, gender, comorbidities score, dialysis vintage and inflammation (CRP > median). In inflamed patients with low fetuin a significantly independent association with mortality (HR 2.3; CI 1.2-4.5, P = 0.01) was observed compared to non-inflamed patients with high fetuin-A, after adjusting for the same variables. Non-inflamed patients with low fetuin-A and inflamed patients with high fetuin-A did not have increased mortality compared to non-inflamed patients with high fetuin-A. CONCLUSIONS: The results show that low levels of serum fetuin-A are associated with increased mortality in HD patients only in the presence of inflammation. This suggests that coexistence of a low serum fetuin-A level and low-grade inflammation exerts an additive effect on the risk of death in HD patients.

The long pentraxin PTX-3 in prevalent hemodialysis patients: associations with comorbidities and mortality.

BACKGROUND: Pentraxin (PTX)-3, a new candidate marker for inflammation is expressed in a variety of cell types. Recently, we have shown that increase in PTX-3 level is associated with clinical outcome in incident CKD stage 5 patients at start of renal replacement therapy. However, no data are available on PTX-3 and its relationship with clinical outcome in prevalent dialysis patients. METHODS: We analyzed plasma PTX-3 concentrations in relation to comorbidities (Davies score), protein-energy wasting (PEW) and inflammation markers in 200 prevalent hemodialysis (HD) patients, aged 64 +/- 14 years, who had been on HD treatment for a median period of 36 months. Survival (42 months) was analyzed in relation to PTX-3 levels (high PTX-3 tertile vs. low two tertiles). RESULTS: Plasma PTX-3 correlated positively with C-reactive protein and interleukin-6, and negatively with s-albumin and fetuin-A. Patients with cardiovascular disease (CVD) and PEW had higher levels of PTX-3 than their counterparts and PTX-3 was associated with comorbidity score. In multiple logistic regression analysis, the high comorbidity score and PEW were the significant predictive variables of high PTX-3. In unadjusted analysis high PTX-3 was significantly associated with all-cause mortality. After adjustment for sex, age, dialysis vintage, comorbidity score, PEW and CRP using the multivariate Cox regression analysis, death rate was still significantly higher in patients with high PTX-3 (HR 1.7; CI 1.1-2.7, P = 0.03). CONCLUSION: Markedly increased levels of PTX-3 were found in HD patients with signs of CVD and PEW. In addition, the concentration of PTX-3 was associated with inflammation markers and comorbidity score. Our data also shows that high PTX-3 level was independently associated with all-cause mortality.

Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease.

OBJECTIVES: In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD). DESIGN: After exclusion of 23 patients with thyroid-stimulating hormone (TSH) values outside the normal range (0.1-4.5 mIU L(-1)), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1-60) months. Measurements of total and free forms of thyroid hormones, s-albumin, hs-CRP, interleukin (IL)-6, vascular adhesion molecule (VCAM)-1 and insulin-like growth factor 1 (IGF-1) were performed at baseline. RESULTS: In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut-off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs-CRP, IL-6 and VCAM-1) and lower concentration of both s-albumin and IGF-1. Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors. CONCLUSION: This study showed that low T3 levels are independent predictors of all-cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.

Low-grade inflammation in chronic kidney disease patients before the start of renal replacement therapy: sources and consequences.

Low-grade inflammation is a common feature of chronic kidney disease (CKD) already before the start of renal replacement therapy, and evidence suggests that persistent inflammation may also be per se a risk factor for progression of CKD and vascular disease. Many factors, including retention of pro-inflammatory cytokines, advanced glycation end products, reactive oxygen species, autonomic dysfunctions and volume overload may contribute to inflammation when renal function declines. The aim of the present review is to summarize the causes and consequences of a chronic inflammatory state in the CKD population before start of renal replacement therapy, with special emphasis in polymorphnuclear leukocyte priming, which may be a key mediator in the induction of a vicious circle of oxidative stress and inflammation in CKD. A more thorough characterization of uremic retention solutes with regard to their specific pro- and anti-inflammatory properties is needed.

Plasma apelin is lower in patients with elevated LDL-cholesterol.

Hypercholesterolemia is a major risk factor for atherosclerosis. Dysregulation of adipokines contribute to atherosclerotic diseases. Apelin has recently been shown to be secreted by the adipose tissue in association with hyperinsulinemia and inflammation. We searched plasma apelin levels in patients with elevated low density lipoprotein (LDL)-cholesterol having no additional disorder. Thirty-three patients with hypercholesterolemia and 50 age-, sex-, and body mass index-matched healthy controls were evaluated for their apelin, adiponectin and high sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment (HOMA) indexes. Plasma apelin-12 and adiponectin were determined by ELISA and RIA, respectively. Plasma apelin levels were lower in patients with elevated LDL-cholesterol compared to healthy controls (p<0.001). Plasma adiponectin concentration was also lower in the dyslipidemic patients (p<0.001). hsCRP levels were similar in the two groups. Fasting plasma glucose was normal in both groups. HOMA indexes in the dyslipidemic group were higher than the controls (p=0.005). A mild to moderate negative correlation with HOMA and positive correlation with high density lipoprotein cholesterol of apelin was found in the dyslipidemic group. Plasma apelin is decreased in non-obese, non-diabetic and normotensive patients with elevated LDL-cholesterol. Low apelin levels in hypercholesterolemia seem associated with insulin resistance, which needs to be investigated in larger populations as well as in other atherosclerotic conditions.

Differentiating effect of thalidomide and FGM-CS combination on HL-60 acute promyelocytic leukemia cells.

AIM: To investigate whether granulocyte-macrophage colony-stimulating factor (GM-CSF) with or without thalidomide can induce apoptosis and differentiation of HL-60 acute promyelocytic leukemia cell line in vitro. METHODS: Effect of GM-CSF and thalidomide on proliferation of HL-60 cells was evaluated by MTT assay, cell cycle analysis was performed by propidium iodide staining approach and flow cytometry, and apoptosis rate was analyzed using FITC-conjugated annexin-V and FACScan flow cytometry. RESULTS: The study revealed that thalidomide alone at high concentrations inhibited HL-60 cell growth and induced apoptosis. Three days treatment of low-dose thalidomide in combination with GM-CSF induced marked terminal differentiation of HL-60 cells, as it was assessed by increased expression of differentiation antigens on cell surface. CONCLUSION: Treatment of HL-60 cells by low concentration of thalidomide combined with GM-CSF induced terminal differentiation of HL60 cells in vitro, which may be advantageous for the elaboration of novel therapeutic regimens in patients with differentiation-inducible leukemias.

The plasma levels of soluble P-selectin in subjects with prediabetes.

Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P-selectin (sP-selectin) is an index of platelet activation and also a risk factor for future vascular events. sP-selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP-selectin, hsCRP levels and HOMA-IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age-, sex- and BMI-matched 40 healthy controls. sP-selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA-IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP-selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP-selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.

ADMA, proteinuria, and insulin resistance in non-diabetic stage I chronic kidney disease.

The rationale of this study is based on the fact that, both proteinuria and elevated asymmetric dimethyl arginine (ADMA) levels have been linked to the progression of vascular disease. Currently, there is not enough knowledge about any association between the levels of proteinuria and ADMA levels. Seventy-eight non-diabetic patients (42 men, 36 women, mean age of 26.1+/-5.2 years) with proteinuria having normal glomerular filtration rate were enrolled along with 38 healthy subjects (20 men, 18 women, mean age of 26.9+/-5.9 years). Proteinuria was below 3.5 g/day in 40 patients and above 3.5 g/day in 38 patients. Both groups had similar age, gender, and body mass index distributions. Serum ADMA, symmetric dimethyl arginine (SDMA), immunoreactive insulin, and high sensitivity C reactive protein (hsCRP) levels were measured. Insulin resistance was determined by homeostasis model assessment (HOMA). Serum ADMA, SDMA, insulin, hsCRP levels, and HOMA indexes were significantly higher in patients than in healthy control subjects. The above parameters were higher in the nephrotic range proteinuria group when compared to patients having protein levels below 3.5 g/day. There were significant correlations between the levels of proteinuria and the above parameters. According to the regression analysis, levels of proteinuria and hsCRP were significant determinants of serum ADMA levels. Our results indicate that, independent of other risk factors, ADMA is directly associated with proteinuria. Further studies are recommended to find out whether elevated ADMA levels are implicated in the high cardiovascular risk of proteinuric nephropathies.

Persistent mediastinal and axillary lymph node tuberculosis in a renal transplant patient with successful outcome.

Tuberculosis is an opportunistic infection that carries substantial morbidity and mortality in renal transplant recipients. We report here about a 21 year-old man with a living related renal transplant from his mother who developed persistent extra-pulmonary tuberculosis. The disease showed aggressive invasion to the axillary and mediastinal regions with abscess formations, despite standard antituberculosis treatment. During the course of the disease, immunosuppressive therapy was stopped, and the patient received extraordinary doses of multiple antituberculosis drugs. The patient then showed an uneventful course with good clinical and radiological responses.

Soluble CD40 ligand levels in patients with hypertension.

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.

Adiponectin level is reduced and inversely correlated with the degree of proteinuria in type 2 diabetic patients.

AIMS: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. METHODS: 80 patients (mean age, 46.9 +/- 5.1 years; body mass index (BMI), 25.8 +/- 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 +/- 5.5 years; BMI 26.74 +/- 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. RESULTS: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 +/- 4.50 microg/ml for patients, n = 47; 24.27 +/- 5.59 microg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 +/- 2.82 microg/ml for proteinuria, n = 37; 11.98 +/- 3.32 microg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = -0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = -0.322, p = 0.004; r = -0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = -0.872, p < 0.001). CONCLUSION: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.

Antioxidant system activation in prostate cancer.

The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the levels of copper, zinc, and malondialdehyde were determined in 21 age-, sex-, and body-mass-index-matched prostate cancer patients; 50 patients diagnosed with benign prostatic obstruction (BPO) were compared to 50 healthy male subjects acting as controls. The patients were divided into two groups depending on the stage of the disease (group 1 [organ-confined] and group II [advanced disease]) and into three subgroups according to differentiation criteria: subgroup A (n = 5, Gleason sum 2-4, well differentiated); subgroup B (n = 9, Gleason sum 5-7, moderately differentiated), and subgroup C (n = 7, Gleason sum 8-10, poorly differentiated). The MDA levels were higher and the antioxidant activity and Zn levels lower in the prostate cancer groups than in the healthy control and BPO groups. These results confirm the value of therapies aimed at increasing the antioxidant capacity and encourage the use of plasma and erythrocyte Zn levels in the differential diagnosis of BPO and prostate cancer. The MDA levels can be used in the diagnosis and follow-up of prostate cancer.

Oxidative stress in patients undergoing high-dose chemotherapy plus peripheral blood stem cell transplantation.

Chemotherapy and radiation therapy are associated with increased formation of reactive oxygen species and depletion of critical plasma and tissue antioxidants. In patients undergoing high-dose chemotherapy, the plasma antioxidant concentration has been shown to decrease. However, these studies in which the oxidative stress status were investigated have a small number of patients and they are heterogeneous. In this study, the changes in certain trace elements together with oxidative stress parameters were investigated in 36 patients who had undergone autologous stem cell transplantation because of solid and hematological malignancies. Blood samples of the patients were examined before the high-dose chemotherapy (baseline), before stem cell transplantation (day -1), and after stem cell transplantation on day 1, 3, and 6. Erythrocyte zinc, silver, and iron levels were measured by atomic absorption spectrophotometry; malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured by UV-vis spectrophotometry. After high-dose chemotherapy, significant increases in the levels of MDA, GSH-Px, and SOD were observed. On the other hand, Cu levels remained the same while the levels of erythrocyte Zn and Fe were increased. Significant correlation was observed among MDA, GSH-Px, and SOD (p<0.05). High-dose chemotherapy gives rise to an increase in the oxidative stress and the reactive oxygen species. Standard parenteral nutrition protocols were found to be insufficient to lower this stress.

Antiannexin V autoantibody in thrombophilic Behçet's disease.

We propose that thrombosis in Behçet's syndrome may be due to disruption of the annexin V shield by antiphospholipid antibodies. Measurement of antiannexin V antibodies may be of value in confirming diagnosis and evaluating the risk of venous and arterial thrombosis in patients with Behçet's syndrome. To evaluate the efficiency of antiannexin V antibody in the formation of thrombosis, 53 male patients with Behçet's disease according to international study group criteria were involved in this study. The age range was 20-28 years (mean 23+/-3.4). All of these patients had been taking colchicum. Those taking medications that interfere with antiannexin V autoantibody levels were excluded, and serum samples were taken during the active period. Group I included 26 Behçet's patients with well-documented thrombosis, group II included 27 Behçet's patients without thrombosis, and group III was comprised of 27 healthy controls. There were no statistical differences between the mean concentrations of IgG and IgM antiannexin V autoantibodies in the three groups. The results indicate that these antibodies may not be associated with the pathogenesis of thrombotic events in patients with Behçet's syndrome.