Renal anemia treatment with ESA in hemodialysis patients in relation to early versus late referral in everyday clinical practice in Central and Eastern European countries: baseline data

The aim of the study was to collect retrospective data on renal anemia management, comorbidities and prospective data on 12-month standard care erythropoiesis-stimulating agent (ESA) therapy used in 398 hemodialyzed patients in selected Central and Eastern European countries (50 centers in 3 countries). Patients were divided into three groups according to ESA therapy start: group A-ESA (after start of hemodialysis, HD), B-ESA (within 3 months from start of HD), C-ESA (more than 3 months before HD). At the chronic kidney disease diagnosis, hemoglobin in all patients was 10.3 ± 2.3 g/dl; however, ferritin, iron, TSAT were within reference limits. Early ESA therapy (C) was administered to 10% of patients only. 47% of patients received ESA after start of dialysis. Before study, the mean weekly ESA dose in group C was statistically lower than in groups B and A (p < 0.001). At baseline visit, hemoglobin in group A patients was slightly lower than in group B and C patients (p = 0.025). In conclusion, in Central and Eastern European countries renal anemia therapy with ESA starts shortly before or after start of HD. This highlights important differences in standard care in Eastern Europe. However, paradoxically, due to the tight reimbursement policy we foresee the clinical implications of the TREAT trial for the chronic kidney disease population.     

Nutritional status and oxidative processes in diabetic and nondiabetic peritoneal dialysis patients.

OBJECTIVE: The purpose of our study was to compare the level of malonyldialdehyde (MDA) and carbonyl groups (GC) in diabetic and nondiabetic peritoneal dialysis patients. DESIGN/SETTING: Prospective, observational study on peritoneal dialysis patients in a teaching hospital dialysis unit. PATIENTS: A total of 21 diabetic and 66 nondiabetic patients treated with peritoneal dialysis were examined in the study. Main outcome measures The assessment of nutritional status was determined by clinical, anthropometric, and biochemical methods. The GC content was determined by the 2,4-dinitrophenylohydrazine assay using the Garibaldi method. The MDA was measured using the colorimetric method (LPO-586). RESULTS: The plasma content of the GC and the MDA of peritoneal dialysis patients was significantly higher than in the healthy group (2.0 +/- 1.3 versus 1.3 +/- 0.4 nmol/mg protein and 3.8 +/- 1.4 versus 3.0 +/- 1.2 micromol/L). Moreover, the tendency toward increased levels of MDA and GC in the diabetic group in comparison with the nondiabetic group was noticed. Also, the highest values of GC and MDA were observed in severely malnourished patients. CONCLUSION: The increase in oxidative stress may be related to a degree of malnutrition.     

Upregulation of fatty acid synthase gene expression in experimental chronic renal failure

Hypertriglyceridemia associated with chronic renal failure (CRF) and elevated plasma concentration of very-low-density lipoprotein (VLDL) are thought to be a consequence of the depressed lipoprotein lipase and hepatic lipase activities and impaired clearance of lipoproteins. However, there is some evidence that the lipoproteins overproduction might also contribute to hypertriglyceridemia in CRF. This study was performed to test the hypothesis that the increased rate of lipogenesis consequent to upregulation of fatty acid synthase (FAS), a key lipogenic enzyme, gene expression could contribute to overproduction of triacylglycerols and to hypertriglyceridemia in CRF. FAS activity, FAS protein mass (Western blot analysis), and FAS mRNA level (Northern blot analysis) in liver and epididymal white adipose tissue (WAT) were measured in male Wistar rats 6 weeks after subtotal (5 of 6) nephrectomy or sham operation. Moreover, the rate of lipogenesis in WAT was determined. The CRF group showed significant increase in FAS gene expression (measured as activity, mRNA, and protein abundance) in both liver and WAT. This was associated with the increase in the lipogenesis rate and with the increase in plasma triacylglycerol and VLDL concentrations. Our results suggest that not only decreased removal, but also an increase of triacylglycerol production could contribute, in part, to the CRF-associated hyperlipidemia. Upregulation of FAS gene expression, shown in this report for the first time, reveals another factor involved in disturbed lipid metabolism in CRF. It seems that elevated plasma insulin and cytokine concentration could play an important role in the mechanism responsible for the increased FAS gene expression in CRF.     

Resolving power to narrow and extended light sources and its influence on legibility of the optotypes

The resolving power of the human visual system has been found to depend on the sizes of the light sources. The sources used in this experiment were two rectangular white fields separated by a vertical black bar, The minimal angle of resolution measured on five subjects decreased by about 10-20 times while the light sources were extended up to the effective range of spatial summation. For larger sources no significant changes of spatial resolution were observed. The experimental data revealed biphasic dependence of the minimal angle of resolution on the sizes of the light sources and permitted estimation of the effective range of spatial summation for 3-9 min arc. This range encompasses the angular diameters of typical optotypes recognized by normal observers (visual acuity greater than 1, optotypes smaller than 5 min arc), therefore we show how the spatial arrangement of the lines and strokes of optotypes determines their legibility.     

Multifactorial determination of hypertensive nephroangiosclerosis

Essential hypertension causes renal injury. Hypertensive nephroangiosclerosis (HN) or hypertensive nephropathy are terms most commonly used to describe this renal pathology. Although specific histological lesions occurring in affected kidneys are well known, pathogenesis of hypertension-related renal scarring is not completely understood. Evidence exists to support the theory that other factors such as aging, black race or smoking, beside blood pressure, contribute to the development and progression of HN. Metabolic disturbances, cocaine and nonsteroidal anti-inflammatory drug abuse, ochratoxin A exposure, dietary salt intake, heavy metal toxicity, hantavirus infection and perinatal programming are also considered risk factors. Renal susceptibility genes may determine whether hypertension-induced progressive renal damage occurs and how severe it is. Determination of all risk factors may identify patients at high risk of renal failure and help tailor an appropriate management. In the present paper, the knowledge available on this clinically important objective is discussed.     

Genotyping of patients with sporadic and radiation-associated meningiomas.

Ionizing radiation is the most established risk factor for meningioma formation. Our aim was to evaluate the main effect of selected candidate genes on the development of meningioma and their possible interaction with ionizing radiation in the causation of this tumor. The total study population included 440 cases and controls: 150 meningioma patients who were irradiated for tinea capitis in childhood, 129 individuals who were similarly irradiated but did not develop meningioma, 69 meningioma patients with no previous history of irradiation, and 92 asymptomatic population controls. DNA from peripheral blood samples was genotyped for single nucleotide polymorphisms (SNP) in 12 genes: NF2, XRCC1, XRCC3, XRCC5, ERCC2, Ki-ras, p16, cyclin D1, PTEN, E-cadherin, TGFB1, and TGFBR2. SNP analysis was done using the MassArray system (Sequenom, San Diego, CA) and computerized analysis by SpectroTYPER. Logistic regressions were applied to evaluate main effect of each gene on meningioma formation and interaction between gene and radiation. Intragenic SNPs in the Ki-ras and ERCC2 genes were associated with meningioma risk (odds ratio, 1.76; 95% confidence interval, 1.07-2.92 and odds ratio, 1.68; 95% confidence interval, 1.00-2.84, respectively). A significant interaction was found between radiation and cyclin D1 and p16 SNPs (P for interaction = 0.005 and 0.057, respectively). Our findings suggest that Ki-ras and ERCC2 SNPs are possible markers for meningioma formation, whereas cyclin D1 and p16 SNPs may be markers of genes that have an inverse effect on the risk to develop meningioma in irradiated and nonirradiated populations.     

DNA adduct formation of benzo[a]pyrene in white blood cells of workers exposed to polycyclic aromatic hydrocarbons

The major DNA adducts of anti-benzo[a]pyrene diolepoxide (BPDE) were determined by high performance liquid chromatography with fluorescence detection (HPLC-FLD) in white blood cells (WBC) of workers exposed to benzo[a]pyrene (B[a]P). In addition, ambient concentrations of B[a]P at the workplace were determined by personal air sampling. Workers in a refractory setting were examined before (n=26) and 3 months after (n = 33) changing the production material (binding pitch). Furthermore, 9 coke oven workers were examined. The change in the production process in the refractory setting led to a decrease in the median of ambient B[a]P concentrations (0.14 to <0.07 microg/m3). The median of BPDE-DNA adduct levels in WBC also decreased from 0.9 adducts/10(8) nucleotides before changing the production material to <0.5 adducts/10(8) nucleotides 3 months afterwards. The B[a]P concentrations at the workplace for the coke oven workers were found to be significantly higher than in the refractory setting. However, BPDE-DNA adduct concentrations in coke oven workers and refractory setting workers showed no significant difference, which was probably due to the low number of studied subjects in the coke-oven setting. No significant differences could be observed for BPDE-DNA adduct levels between current smokers (n=21) and non-smokers (n=14; p = 0.93) from both plants. In addition, no correlation between B[a]P concentrations in the air and DNA adduct levels in refractory workers and in coke oven workers could be found (r = -0.03, p = 0.87). Because of the missing correlation between personal air sampling and BPDE-DNA adduct levels in WBC, the results may indicate that their formation is either influenced by other routes of exposure to B[a]P (e.g., skin absorption, dietary habits) or interindividual differences in their formation and repair.     

Irritative effects of fumes and aerosols of bitumen on the airways: results of a cross-shift study

Possible health hazards of fumes and aerosols of bitumen are in discussion, and data on their adverse effects on human airways under current exposure conditions are limited. To assess the irritative effects of exposure to fumes and aerosols of bitumen on the airways, a cross-sectional cross-shift study was conducted including external and internal exposure measurements, spirometry and especially non-invasive methods like nasal lavage collection and induction of sputum in order to identify and evaluate more precisely inflammatory process in the upper and lower airways. The cross-shift study comprised 74 mastic asphalt workers who were exposed to fumes and aerosols of bitumen and 49 construction workers without this exposure as reference group. Questionnaire, spirometry, ambient monitoring and urinary analysis were performed. Humoral and cellular parameters were measured in nasal lavage fluid (NALF) and induced sputum. For data analysis, a mixed linear model was performed on the different outcomes with exposure group, time of measurement (pre-, post-shift), current smoking, German nationality and age as fixed factors and subjects as random factor. Based on personal exposure measurements during shift, mastic asphalt workers were classified into a low (< or =10 mg/m(3); n = 46) and a high (>10 mg/m(3); n = 28) exposure group. High exposure was accompanied by significant higher urinary post-shift concentrations of 1-hydroxypyrene and the sum of hydroxyphenanthrenes. Acute respiratory symptoms were reported more frequently in the high exposure group after shift. Significant cross-shift declines in lung function parameters (forced expiratory volume in 1 s [FEV(1) (% predicted)] and forced vital capacity [FVC (% predicted)]) were measured in mastic asphalt workers. Pre-shift FEV(1) (% predicted) and FVC (% predicted) were higher in the low exposure group. In pre- and post-shift NALF samples, interleukin (IL)-1beta-, IL-8- and total protein concentrations were lower in the low exposure group compared to the reference and the high exposure group. Pre- and post-shift neutrophil percentages in both nasal and sputum samples were also lower in the low exposure group. Significantly higher pre- and post-shift sputum concentrations of IL-8, IL-6, nitrogen oxide (NO) derivatives and total protein were detected especially in highly exposed workers. Irritative effects of exposure to fumes and aerosols of bitumen on the upper and lower airways were apparent, especially in mastic asphalt workers with exposure above 10 mg/m(3).     

Irritative effects of vapours and aerosols of bitumen on the airways assessed by non-invasive methods

Irritative effects caused by vapours and aerosols of bitumen were assessed by non-invasive methods including spirometry, nasal lavage fluid (NALF) and induced sputum (IS) in a cross-shift study comparing 320 bitumen-exposed workers with 118 road construction workers as the reference group. Lung function parameters, forced vital capacity (FVC) and forced expiratory volume in one second (FEV(1)) were within normal ranges in both the reference and the bitumen-exposed groups pre- and post-shift with marginally lower values in smokers of both groups. During the shift, a slight decline in FEV(1) and FVC was observed in the bitumen-exposed group independent of their smoking habits, whereas in the non-smoking reference group, the decline in FEV(1) was not observed. No significant differences between bitumen-exposed workers and the reference group and no significant shift effect were observed on the upper airways using NALF analysis. The IS concentrations of interleukin (IL)-8, total protein and matrix metalloproteinase-9 were significantly higher in bitumen-exposed workers than in the reference group. However, the concentration of these three biomarkers in the IS samples, which are indicators of inflammatory effects on the lower airways of bitumen-exposed workers, was already higher in exposed workers before shift and did not show an increase during the shift. Therefore, the key finding of this aspect of the Human Bitumen Study is the detection of potentially (sub-) chronic irritative inflammatory effects in the lower airways of bitumen-exposed workers.