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Background and aims Dairy products are a very diverse food group with multiple effects on the cardiac health of men and women. The aim of this work was to evaluate the sex-specific association between dairy products (total and subtypes) and 10-year first fatal/nonfatal cardiovascular disease (CVD) incidence. Methods and results In 2001–2002, n = 1514 men and n = 1528 women (>18 years old) from greater Athens area, Greece, were enrolled. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Dairy product consumption was examined in relation to 10-year CVD incidence. Follow-up (2011–2012) was achieved in n = 2020 participants (n = 317 CVD cases). Ranking from lowest ( 2 servings/day) total dairy intake, CVD incidence in men was 17.8%, 15.0%, and 10.9% (p = 0.41), while in women it was 14%, 6.0%, and 5.7% (p = 0.02). Multiadjusted analysis revealed that total dairy intake protected against CVD only in women [Hazard Ratio (HR) = 0.48 and 95% Confidence Interval (95% CI) (0.23, 0.90)], irrespective of the fat content. Further analysis revealed that only fermented products (yogurt and cheese), protected against CVD. For per 200 g/day yogurt consumption, CVD risk was 20%–30% lower with this claim being more evident in women, while for per 30 g/day cheese intake, about 5% lower risk was observed particularly in men. As for butter, nonsignificant associations were highlighted. These associations were mainly retained in the case of hepatic steatosis, insulin resistance, and systemic inflammation. Conclusions This work provides incentives for researchers to elucidate the diversity of ingredients and mechanisms through which dairy products exert their effect on cardiac health separately for men and women.

Background: Glycated hemoglobin A1c (HbA1c) among diabetic hemodialysis patients continues to be the standard of care, although its limitations are well recognized. This study evaluated glycated albumin (GA) and glycated serum protein (GSP) as alternatives to HbA1c in detecting glycemic control among diabetic hemodialysis patients using continuous-glucose-monitoring (CGM)-derived glucose as reference standard. Methods: A CGM system (iPRO) was applied for 7 days in 37 diabetic hemodialysis patients to determine glycemic control. The accuracy of GA and GSP versus HbA1c in detecting a 7-day average glucose ≥184 mg/dL was evaluated via receiver-operating-characteristic (ROC) analysis. Results: CGM-derived glucose exhibited strong correlation (r = 0.970, p < 0.001) and acceptable agreement with corresponding capillary glucose measurements obtained by the patients themselves in 1,169 time-points over the 7-day-long CGM. The area under ROC curve (AUC) for GA, GSP, and HbA1c to detect poor glycemic control was 0.976 (0.862–1.000), 0.682 (0.502–0.862), and 0.776 (0.629–0.923) respectively. GA levels >20.3% had 90.9% sensitivity and 96.1% specificity in detecting a 7-day average glucose ≥184 mg/dL. The AUC for GA was significantly higher than the AUC for GSP (difference between areas: 0.294, p < 0.001) and the AUC for HbA1c (difference between areas: 0.199, p < 0.01). Conclusion: Among diabetic hemodialysis patients, GA is a stronger indicator of poor glycemic control assessed with 7-day-long CGM when compared to GSP and HbA1c.

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.

Objectives The aim of this study was to compare lung deposition and assess the bioequivalence of two formulations containing budesonide and formoterol and being delivered via Elpenhaler and Turbuhaler, respectively. A pharmacokinetic (PK) study was conducted. Methods An open, randomized, two-sequence, two-period, crossover, single-dose study in 100 asthmatic patients under fasting conditions was performed. Wash out period was 6 days. Equivalence in lung deposition was assessed after a single inhalation of each treatment with concomitant oral administration of activated charcoal (40 g) to prevent gastrointestinal absorption of the drugs. Several PK parameters were estimated, the area under the drug concentration in plasma versus time curve (AUC0−t) and the maximum drug concentration in plasma (Cmax) being the primary response variables. Equivalent lung deposition was concluded if the 90% confidence interval (CI) for the Elpenhaler/Turbuhaler geometric mean ratio of AUC0−t and Cmax, for both drug substances fell within the regulatory limits (0.80–1.25). Key findings Acceptance criteria were met. Equivalent lung deposition can be concluded. No statistically significant differences between treatments in the incidence of adverse events were found. Conclusions The formulations are bioequivalent regarding both rate and extent of absorption. The treatments were also well tolerated by the participating subjects.

Background/Aims: In experimental models of polycystic kidney disease impaired bioavailability of nitric oxide (NO) and elevated mRNA expression of oxidative stress markers at the kidney level was noted. However, clinical studies investigating the potential role of endothelial dysfunction and oxidative stress in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are limited. We evaluated asymmetric dimethylarginine (ADMA) as marker of NO synthase inhibitor as well as 15-F2t-Isoprostane and oxidized-low density lipoprotein (oxidized-LDL) as measures of oxidative stress in patients with early stages ADPKD. Methods: We recruited 26 ADPKD patients (Group A) with modestly impaired renal function (eGFR 45-70 ml/min/1.73m2), 26 age- and sex-matched ADPKD patients (Group B) with relatively preserved renal function (eGFR)>70 ml/min/1.73m2), and 26 age- and sex-matched controls (Group C). Determination of circulating levels of ADMA, 15-F2t-Isoprostane, oxidized-LDL and routine biochemistry was performed. Results: Group A and B had significantly higher ADMA levels as compared to controls (1.68±0.7 vs 0.51±0.2 μmol/l, P2t-IsoP and oxidized-LDL levels were also significantly higher in Group B relative to controls (788.8±185.0 vs 383.1±86.0 pgr/ml, P2t-Isoprostane (r=0.811, PConclusion: This study shows elevation in circulating levels of ADMA along with aggravation of oxidative stress from the early stages of ADPKD.

Noninvasive screening studies may identify hemodialysis (HD) patients at increased risk of sudden cardiac death. Interventions that improve the findings of such screening studies may reduce sudden cardiac death.Randomized and controlled clinical trial.59 HD patients were randomly assigned to an exercise training group (group A; 30 patients) or control group (group B; 29 patients).Group A participated in a 10-month supervised exercise training program during the HD sessions (3 times weekly).Each risk factor separately and the composite risk score. Patients were considered high risk according to the criteria (aerobic capacity: peak oxygen consumption [Vo(2)peak]or = 14 mL/kg/min, left ventricular ejection fractionor = 30%, SD of normal RR intervals [SDNN]or = 70 milliseconds, positive T-wave alternans, or positive late potentials). Statistical analysis included a 2-group comparison of change scores and analysis of covariance adjusting for baseline.At entry and end of the study, Vo(2)peak and left ventricular ejection fraction were estimated, heart rate variability was calculated (measurement of SDNN, mean RR intervals), and the ratio between low- (LF) to high-frequency (HF) components (LF/HF) and late potentials and T-wave alternans were detected.Baseline measurements were similar between the 2 groups. At follow-up, 9 patients from group A and 20 from group B (P = 0.003) were considered high risk. The change in number of risk markers over time was significantly different between groups (-0.5 +/- 0.7 in group A versus 0.07 +/- 0.3 in group B; P0.001). Additionally, the change in Vo(2)peak over time was 3.5 +/- 3.2 in group A and -0.2 +/- 3.5 mL/kg/min in group B (P0.001), left ventricular ejection fractions were 3.4% +/- 3.9% and 0.2% +/- 7.7% (P0.05), SDNNs were 12.6 +/- 16.3 and -1.1 +/- 10.2 milliseconds (P0.001), and LF/HF ratios were 0.3 +/- 0.4 and -0.1 +/- 0.3 (P0.001), respectively. Change in numerical score of the signal-averaged electrocardiogram also was found to be statistically different (P0.05) between groups.Clinical outcomes, including survival, were not assessed.Exercise training improves aerobic capacity and ameliorates some indicators of risk of sudden cardiac death in HD patients.

ObJEct IVE: t he aim of this study was to evaluate the changes in the levels of vasoactive eicosanoid hormone-like substances PGE 2, PGI2 and t XA2 in hemodialysis (HD) patients who were following a long-term physical training program during the hemodialysis session. DE sIGN: A total of 50 patients with c hronic Kidney Disease ( c KD) (stage 5) on hemodialysis and 35 healthy individuals who served as controls ( c ) were evaluated. t he 50 c KD patients were divided into two groups: the HD group consisted of 31 patients who received usual care without any physical activity during the hemodialysis sessions, while group HD/Exer included 19 patients who followed a program of physical exercise for six months. Plasma levels of PGE 2, 6-Keto-PGF1α (the stable derivative of PGI 2) and t Xb 2 (the stable derivative of t XA2) were measured by reliable enzymo-immunoassay methods (EIA) in HD and HD/Exer patients before and after the hemodialysis sessions as well as in the group of c . rEsULts : t he plasma levels of PGE 2 and 6-keto-PGF1α in group HD Exer/ before patients were higher than those in group HD before (20.39±5.82 and 1449.19±553.41 vs 17.68±5.36 and 1295.10±384.43 pg/ml, p=0.044 and p=0.067, respectively), while the plasma levels of t Xb 2 were lower in HD Exer/ before patients compared to HD before(499.76±67.51 vs 608.01±80.23 pg/ml, p=0.041). t he plasma levels of PGE2 and 6-keto-PGF1α in group HD Exer/ after patients were significantly higher compared to those in HDafter patients (23.01±5.70 and 1618.19±435.07 vs 16.57±4.97 and 1005.44±317.16 pg/ ml, p

Objective: To assess the effects of intradialytic exercise training on health-related quality of life indices in haemodialysis patients.Subjects/patients: Thirty-five patients on haemodialysis, with a mean (SD) age of 48.8 (13.9) years, volunteered to participate in the study. They were randomized either to rehabilitation group (group A: 19 patients), following a 10-month intradialytic exercise training programme or to control group (group B: 14 patients). After the randomization, two of the patients, one of each group, withdrew from the study for reasons unrelated to exercise training.Method: All patients at the beginning and the end of the study underwent clinical examination, laboratory tests and a treadmill exercise testing with spiroergometric study for the evaluation of their aerobic capacity (Vo2peak). A formal psychosocial assessment, which included affective (Beck Depression Inventory), health-related quality of life (Quality of Life Index, Living Questionnaire of Minnesota, Life Satisfaction Index and Short Form-36 questionnaire) and personality (Eysenck Personality Questionnaire) parameters, was evaluated at beginning and end of the study. The dose of erythropoietin was changed as needed, according to the level of the haemoglobin, aiming to keep it at 11 (2) g/dL during the study.Results: Baseline values were similar between the two groups. After training in group A, Vo2peakwas increased by 21.1% (PConclusion: The results demonstrated that intradialytic exercise training improves both physical functioning and psychological status in haemodialysis patients, leading to an improvement of patients' quality of life.

Background: Arterial baroreflex sensitivity (BRS) evaluation has been increasingly used as an index of cardiac autonomic control. Cardiac autonomic dysfunction leading to depressed BRS has been associated with an increased risk of ventricular arrhythmias and sudden death in patients with chronic kidney disease (CKD) on hemodialysis (HD). Aim: The purpose of this study was to investigate the effects of an exercise training program during hemodialysis on BRS in CKD patients. Patients and methods: 43 HD patients participated in the study. They were randomly assigned into either a 7-month exercise training program during HD (Group A: n = 22 patients) or a sedentary control group (Group B: n = 21 patients). Additionally, 20 sex- and age-matched sedentary individuals comprised a healthy control group (Group C). All patients at the beginning and the end of the study underwent a tilt test for evaluation of BRS and an exercise testing with spiro-ergometric study for cardiorespiratory capacity estimation. The level of Hb, medications and the HD procedure remained stable during the study. Results: At baseline BRS was found to be reduced by 51.5% (p < 0.05) and baroreflex effectiveness index (BEI) by 36.4% (p < 0.05) in Group A compared with Group C. Initially, all HD patients had also significantly lower exercise time and VO 2 peak than the healthy subjects. After training, Group A showed a significant improvement in BRS by 23.0% (p < 0.05), in BEI by 27.0% (p < 0.05), in event and ramp count by 35.0% (p < 0.05) and 29.0% (p < 0.05), respectively as well as in VO 2 peak by 22.4% (p < 0.05) and in exercise time by 40.9% (p < 0.05). Significant correlations were found between BRS and METS (r = 0.476, p < 0.05), BRS and VO 2 peak (r = 0.443, p < 0.05), BEI and METs (r = 0.492, p < 0.05), BEI and VO 2 peak (r = 0.467, p < 0.05), event count and VO 2 peak (r=0.715,p

Background/Aims: Increased oxidative stress in chronic kidney disease (CKD) was suggested to be both a cause and an effect of renal injury. However, the evolution of oxidant stress from early stages of renal function decline is not fully clear. This study aimed to determine the oxidant-antioxidant balance across the whole range of renal function. Methods: A total of 116 patients with CKD (85 predialysis patients divided into groups according to CKD stage, and 31 patients with end-stage renal disease (ESRD) on hemodialysis treatment), as well as 29 healthy subjects were evaluated. Plasma levels of 15-F2t-isoprostane (15-F2t-IsoP), a valid marker of oxidant stress, as well as total antioxidant capacity (TAC) and serum levels of vitamin E were measured in all participants. Results: Plasma 15-F2t-IsoP levels were higher in predialysis and ESRD patients compared to healthy subjects and were progressively increasing with advancing CKD stages (p < 0.001). In contrast, plasma TAC was similar between healthy subjects and predialysis patients, and presented a small reduction in ESRD patients (p < 0.001). Vitamin E levels were higher in healthy subjects compared to any other group (p < 0.001) and slightly higher in ESRD patients compared to predialysis patients (p < 0.01), but did not differ significantly between the groups of predialysis patients. Plasma 15-F2t-IsoP levels were inversely correlated with estimated glomerular filtration rate in predialysis patients (r = –0.65, p < 0.001). Conclusions: This study shows that 15-F2t-IsoP levels increase progressively with advancing CKD stages, whereas TAC and vitamin E levels remain rather stable with the loss of renal function and change only in patients with ESRD.

Digital clubbing due to secondary hyperparathyroidism has been described as an unusual complication among patients with chronic kidney disease undergoing maintenance hemodialysis therapy. Although the pathogenesis of digital clubbing is unknown, certain growth factors such as platelet-derived growth factor and hepatocyte growth factor have been associated with this clinical syndrome. Two patients of our renal unit population presented this unique clinical feature bilaterally, among the other clinical findings of severe secondary hyperparathyroidism. Both patients were subjected to parathyroidectomy. Histological examination revealed diffuse hyperplasia of parathyroid glands. Despite the improvement of clinical symptoms and laboratory findings of secondary hyperparathyroism after parathyroidectomy, digital clubbing remained unchanged.

Background/Aims: Fast intravenous (i.v.) iron administration during hemodialysis (HD) is associated with the augmentation of oxidative stress and the increase in inflammatory biomarkers, which are also induced by the hemodialysis procedure itself. The aim of this study was to investigate if slow i.v. iron administration would aggravate the status of oxidative stress and inflammatory biomarkers during a hemodialysis session. Methods: Twenty dialysis patients 30–92 years of age that were iron replete and had values for hemoglobin, transferrin saturation and serum ferritin among recommended goals were evaluated in three separate hemodialysis sessions. In the first session patients did not receive any iron treatment, whereas during the second and the third session patients received slow (60 min) i.v. infusions of 100 mg of iron sucrose and 100 mg of iron dextran, respectively. Blood samples were drawn before the hemodialysis session, 15 min after the end of iron administration and at the end of the hemodialysis session in all occasions, for the measurement of markers of oxidant stress (oxidized LDL and ischemia-modified albumin) and inflammation (high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-α). Results: Oxidized LDL was not significantly altered during hemodialysis and this pattern was similar between the three occasions studied. In contrast, ischemia-modified albumin was significantly increased and this effect was also not different between the net hemodialysis and the occasions of iron administration. High-sensitivity CRP, IL-6 and TNF-α were all significantly elevated during hemodialysis and again both types of iron administration did not produce significant changes in this pattern. Conclusion: We did not find an increase in the markers of oxidation/inflammation studied, after slow i.v. iron administration during hemodialysis session.

The purpose of this work was to investigate the links between oxidative stress, inflammation and coagulation and their effect on Mediterranean diet-diabetes relationship.In 2001-2002, a random sample of 1514 men (18-87 years old) and 1528 women (18-89 years old) was selected to participate in the ATTICA study, where Athens is the major metropolis. A validated questionnaire was used to assess lifestyle and dietary factors. Adherence to Mediterranean diet was recorded using MedDietScore. Among others, oxidative stress and inflammatory biomarkers were recorded. During 2011-2012, the 10-year follow-up was performed. Diabetes incidence was defined according to the American Diabetes Association criteria.A total of 191 incident cases of diabetes were documented, yielding an incidence of 12.9% (13.4% in men and 12.4% in women). Medium and high adherence was found to decrease diabetes risk by 49% (95% CI: 0.30, 0.88) and 62% (95% CI: 0.16, 0.88), respectively, compared with low adherence. A logarithmic trend between Mediterranean diet and diabetes incidence was also revealed (p for trend = 0.042). Individuals with abnormal waist circumference (94 for men,80 for women) were benefited the most. Wholegrain cereals, fruits and legumes had the greatest predictive ability. The anti-diabetic effect of Mediterranean diet correlated with measurements of tumour necrosis factor-α, homocysteine and total antioxidant capacity.The reported results support the role of Mediterranean diet as a promising dietary tool for the primary prevention of diabetes, by attenuating inflammation and fostering total antioxidant capacity. This dietary pattern may have therapeutic potential for many cardiometabolic disorders associated with inflammation and/or oxidative stress.

Background: Atherosclerotic cardiovascular events are a major cause of morbidity and the main cause of mortality in hemodialysis patients. Hyperhomocysteinemia – which is a consistent finding in uremic patients – is considered an independent risk factor for cardiovascular disease (CVD). However, the relationship between plasma homocysteine (Hcy) concentrations and atherosclerotic CVD has not been extensively investigated. Patients and Methods: 37 patients undergoing chronic hemodialysis and 30 healthy individuals (control group), sex- and age-matched, were included in this study. Both healthy controls and hemodialysis patients underwent echo-Doppler carotid artery examination. The right and left carotid arteries were assessed separately. Our observation included measurements of the ultrasound images of the intimal wall thickness, the lumen diameter and the atherosclerotic plaques. We determined plasma Hcy, vitamin B12 and folic acid levels and serum cholesterol, triglycerides, HDL, ApoA-I, ApoB-100, Lp(a), CRP, albumin and creatinine levels in blood samples from both studied groups. We also determined the urea reduction ratio in the patient groups. The epidemiological as well as the biochemical data were correlated with the findings of the carotid artery examination. Results: Plasma Hcy levels were significantly increased in hemodialysis patients compared to controls (33 ± 12.3 vs. 12.27 ± 7.47 µmol/l, p < 0.001). Intimal wall thickness, lumen diameter and number of atherosclerotic plaques of both carotid arteries were significantly higher (p < 0.01 or p < 0.001) in patients compared to controls. There was a significant positive correlation between plasma Hcy levels and the number of the atherosclerotic plaques (r = 0.41, p < 0.01 in the right and r = 0.49, p < 0.001 in the left carotid artery). Lumen diameter was significantly (p < 0.01) associated with age, MAP and CRP levels. Significant correlations (p = 0.05–0.01) were also found between the number of the plaques and age as well as the duration of hemodialysis, while folic acid levels were inversely correlated with the number of the plaques. Conclusions: Both hyperhomocysteinemia and atherosclerotic indices of the carotid arteries are more prevalent in hemodialysis patients compared to healthy controls. Elevated plasma Hcy levels were associated with the carotid artery atherosclerotic indices in chronic hemodialysis patients.

8-Iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a characteristic F2-isoprostane which is produced in humans via a free radical-catalysed lipid peroxidation mechanism of arachidonic acid, independent of the cycloxygenase pathway. The measurement of the plasma levels of 8-iso-PGF2alpha was shown to be the most reliable biochemical index of oxidant stress status in the human body. However, there is no reference in literature of local muscle interstitial 8-iso-PGF2alpha production during dynamic muscle contractions. The aim of the present study was to evaluate the response of 8-iso-PGF2alpha during intensive exercise with a cycle ergometer. Two microdialysis probes with CMA-60 microdialysis catheters were inserted into the vastus lateralis muscle of the right leg of six healthy male volunteers. After insertion, these microdialysis probes were attached to a perfusion pump that perfused ringer acetate solution at a rate of 0.3 microl/min. The dialysate fluid samples were collected: (a) during a 30 min rest period and (b) during a 30 min period of dynamic exercise with a cycle ergometer at 150 Watts. Our measurements showed that the levels of 8-iso-PGF2alpha in the interstitial fluid (IF) of the vastus lateralis muscle increase significantly during exercise (from 113.5 +/- 30.2 to 329.9 +/- 69.8 pg/ml, P = 0.05). In conclusion, dynamic muscle exercise produces a local increase of the IF levels of 8-iso-PGF2alpha due to local peroxidation injury of the contractive muscle. The microdialysis method is widely applied, easily repeated and it could contribute in evaluating the local lipid muscle peroxidation during intensive exercise.

Twenty-five brachial-basilic arteriovenous (AV) fistulas with transposed basilic vein for alternative vascular access were created in 22 chronic hemodialysis patients. This surgical procedure was performed under brachial block or general anesthesia. After a longitudinal skin incision that was made in the inner side of the arm, the basilic vein was exposed, transposed subcutaneously, and anastomosed end-to-side to the brachial artery. The follow-up was between 7 and 24 months. Early complications were hemorrhage, thrombosis, steal syndrome, and swelling of the arm. Among the late complications were failure of the fistula because of thrombosis and multiple stenosis at the site of venipuncture. The accumulated one-year patency rate of fistulas was 81%. The complications of high-output cardiac failure or local infection were not seen in our study. On the basis of our results, the brachial-basilic AV fistula with transposed basilic vein is a useful and safe second- or third-choice vascular procedure for hemodialysis patients, in particular for women without good quality of vessels.

Persistent left superior vena cava represents a congenital venous anomaly that poses a particular obstacle to the implantation of cardiac rhythm management devices. In the present report we briefly describe the rightsided implantation of a biventricular defibrillator in a patient with persistent left superior vena cava. We also briefly discuss the technically challenging procedures applied in such cases.

The aim of the present study was: (a) to assess the effect of HBsAg on the survival of both renal grafts and patients, and (b) to determine the outcome of HBV chronic infection after renal transplantation. Fourteen patients seropositive for HBsAg but asymptomatic before renal transplantation (group A) were included in the study. The results were compared to those of 14 transplanted patients (group B) seronegative for HBsAg with similar age and immunosuppressive treatment. Four patients received a graft from a living-related donor and 10 patients from a cadaver donor in each group. Eight of 14 patients of group A showed, after renal transplantation, chronic hepatitis, which was not observed in any of the group B patients (p < 0.01). The rate of acute rejection episodes was significantly greater (p < 0.05) in group B than in group A. The graft survival was found to be similar in both groups at the 1st year, but significantly less (p < 0.01) in group B than in group A at the 5th year after transplantation. The survival of patients was found to be significantly less in group A than in group B at the 1st (p < 0.05) and 5th years (p < 0.01) after transplantation. In 2 patients of group A and 1 of group B anti-HCV was found, while HDAg plus anti-HD was found in 1 patient of group B. The HBV-DNA was found in 4 of 8 alive patients of group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim: The aim of this study was to examine the validity, reproducibility and internal consistency of a Greek translation of the Kidney Disease Quality of Life-Short Form (KDQOL-SF) questionnaire. Methods: The KDQOL-SF questionnaire was translated from English to Greek and was administered in 240 randomly selected patients undergoing hemodialysis in six Renal Units in Greece. The instrument’s validity was tested by examining the association between patient’s KDQOL-SF scores and comorbidity assessed with the Index of Coexistent Disease. Reproducibility was examined by readministering the questionnaire in 50 randomly selected patients within 1 month. Internal consistency was assessed by estimating Cronbach’s alpha coefficient. Results: Patients were divided into two groups according to the severity of comorbidity assessed with the Index of Coexistent Disease. Those with less comorbid conditions had significantly higher scores in most components of the KDQOL-SF questionnaire, confirming its validity. The correlation coefficients between the two administrations of the instrument ranged from 0.88 to 0.98 for each of the main components, which was above the desired level of 0.85. Cronbach’s alpha coefficient ranged from 0.91 to 0.92 for the various components, values well above the minimum desired 0.70 level. Conclusions: The present study shows that the Greek version of the KDQOL-SF questionnaire has high validity, reproducibility and internal consistency. Production of validated translations of the KDQOL-SF questionnaire in various languages will help promote health-related quality of life of end-stage renal disease patients all over the world.

South Med J

Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease. The Homocysteine Lowering Trialists' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25%. Aim of this study was to investigate the effect of daily supplementation of folic acid (5 mg) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor.We enrolled 103 patients with at least one cardiovascular risk factor who were randomized to receive either a daily dose of 5 mg folic acid (group I, n=53) or placebo (group II, n=50) for 18 months.After 18 months of folic acid supplementation, homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group. Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter. Significant regression of carotid IMT was observed (0.961+/-0.092 to 0.933+/-0.077 mm, p0.001) compared to significant IMT progression in the placebo group (0.964+/-0.099 to 0.984+/-0.094 mm).Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk.

OBJECTIVE: The concentration of 8-iso-prostaglandin-F2α (8-iso-PGF2α) in biological fluids has been considered as the most reliable biochemical index of the lipid peroxidation and oxidative stress in patients with several pathological conditions including end stage renal failure. However, there is no reference regarding the influence of hemodialysis (HD) on the values of 8-iso-PGF2α in the muscle Interstitial Fluid (IF) of patients with end stage renal failure. The aim of our study was to determine 8-iso-PGF2α concentration in the IF during hemodialysis and the gradient between plasma and IF in patients with end stage renal failure. DESIGN: In this study, two microdialysis probes were inserted into the vastus lateralis muscle of the right leg of six male patients with end stage renal failure who were on hemodialysis, and in six healthy males (controls). The samples of IF (12 dialysate fluids) were collected after an equilibration of 30 min: a) during the 1st hour preceding hemodialysis (group CRF0), b) during the 1st, 2nd, 3rd and 4th hour while on hemodialysis (groups CRF1, CRF8, CRF3 and CRF4) and c) during the 1st hour following hemodialysis (group CRF5). At the end of the above periods and simultaneously, blood samples were drawn from the arteriovenous fistula. In the controls, the IF samples (twelve dialysate fluids) were collected during a period of one hour and the blood samples at the end of this period. The levels of 8-iso-PGF2α were measured with an enzyme-immunoassay method. Statistical evaluation was carried out with the statistical program NCSS 2000 and the ANOVA test. RESULTS: Plasma and IF levels of 8-iso-PGF2α in the patients were significantly higher than in controls at base line. During hemodialysis, the 8-iso-PGF2α rose progressively both in plasma and IF but remained higher in plasma than in IF. CONCLUSIONS: Lipid peroxidation is higher in patients on hemodialysis than in controls but it is lower in the IF compared to plasma. The mechanism for this gradient is speculative.

Exercise training has been shown to improve the low functional capacity and quality of life in dialysis (HD) patients. However, there are no data about the outcome of long-term exercise training and, also, the adherence of HD patients in such long-term renal rehabilitation programs. Therefore, the aim of this study was to evaluate the effects of 2 modes of long-term physical training on HD patients' physical fitness, perception of health and overall life situation.Forty-eight HD patients, free of any other systemic disease, who followed 2 modes of exercise training for 4 years, were studied. Half of them (group A) were randomly assigned to participate in a supervised outpatient exercise training program (3/weekly) on the non-dialysis days, while the other half (group B) followed a training program with stationary bicycles during their HD sessions (3/weekly). The measured domains of physical fitness and well-being every year were: aerobic capacity, as estimated from a modified Bruce treadmill exercise test and spiroergometric study, the patients' perception of health, the overall life situation and the employment status.During the 4-year study, there were 8 drop-outs in group A and 5 in B. No adverse effects of the exercise programs were reported. The 1 year of exercise training resulted in 38% in group A (16 patients, who remained in the study) and 31% in group B (18 patients) improvement of exercise time, and a 47% increase in group A of peak oxygen consumption (VO2peak) and a 36% in group B in comparison to baseline value. After 3 additional years of training, significant improvements were also noted in exercise time (by 53% in group A and by 43% in B) and VO2peak (by 70% in group A and by 50% in group B), as well as in other gas exchange variables in comparison to baseline values. However, the improvements in group A were more pronounced than in B. Interestingly, the gains in exercise capacity were more enhanced in the first year of training in both groups. After 4-year training, significantly more patients in both groups perceived their health and overall life situation as well, compared to baseline. In addition, perception of improved health was higher in group A. The increase in the proportion of patients working was also higher in group A than B after the 4-year training.HD patients can adhere to long-term physical training programs on the non-dialysis days, as well as during hemodialysis with considerable improvements in physical fitness and health. Although training out of HD seems to result in better outcomes, the drop out rate was higher.

Studies in experimental models of renal ischemia have shown that calcium antagonists are effective in the protection from the ischemic insult. Thirty-five patients who received a kidney graft over a 2-year period (nifedipine group) were compared with 35 consecutive transplanted patients (control group). The two groups were compatible with regard to age, sex, duration of hemodialysis, graft matching, and total number of blood transfusions. The patients in the nifedipine group were given 0.2 mg nifedipine (10% solution) through the renal artery immediately after revascularization, and also nifedipine per os during all the study periods. Adequate diuresis (1 mL/min) was obtained in 14.5 +/- 37.2 and 43.9 +/- 46.8 h after transplantation in the nifedipine and control groups respectively (p0.01). The frequency of acute tubular dysfunction and the mean serum creatinine concentrations were found to be higher in the control group. Fractional excretion of sodium was not found to be different in the two groups on the first day, but it was significantly lower by the first week after transplantation in the nifedipine group (p0.05). Acute rejection episodes were found to be more frequent in the control group during the first 6 months after transplantation (p0.05). It is suggested that nifedipine is effective in the protection of renal function after transplantation.

Background: The most common cause of post-transplant dyslipidemia is the use of corticosteroids and cyclosporin-A (CyA). The HMG-CoA reductase inhibitors have emerged as the agents of first choice in the treatment of post-transplant hyperlipidemia in combination with low fat diet. The objective of this study was to evaluate the efficacy of combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia. Patients and Methods: Twenty-four renal transplant patients, 15 men and 9 women aged from 30 to 60 years with stable renal function were included in this study. All patients were transplanted from living related donors and were given a stable triple immunosuppressive therapy, with methylprednisolone, azathioprine and CyA. All patients were also given a standard diet containing 1 g/kg BW protein, reducing the daily fat to less than 30%, and maintaining at least a 1:1 ratio of saturated to polyunsaturated (or monounsaturated) fats. A dosage of 20 mg pravastatin (pravachol) and 1 g of fish oil (prolipid) were added to the diet after dinner, according to our protocol. Blood samples were taken after each study period for total cholesterol, LDL-cholesterol, triglycerides, Apo A1, Apo B, Lp(a), creatinine, CPK and fibrinogen determination. Results: At the end of the therapeutic protocol with pravastatin a significant reduction (p < 0.02) of total and LDL-cholesterol was observed, but no significant change in triglycerides, HDL, Lp(a), Apo A1, Apo B and fibrinogen was shown. At the end of the therapeutic protocol with pravastatin and fish oil supplement significant changes were seen in TC (p < 0.02), TG (p < 0.03), LDL-C (p < 0.03), Apo A1 (p < 0.04) and Apo B (p < 0.05) concentrations. There were no significant changes in HDL-C and Lp(a) concentrations. Renal function and cyclosporine levels were not changed during and after the study. CPK was increased only in one case. Conclusions: It is suggested that if the response to the diet is inadequate, the use of combined treatment with low-dose pravastatin and fish oil is a more effective strategy than the pravastatin treatment alone for changing the lipid profile after renal transplantation.

Hypertension accounts for 65 - 85% of patients beginning dialysis, and dialysis alone controls hypertension in over 50% of patients.We have surveyed the status of BP control in 113 hemodialysis patients, 66 men and 47 women, aged 59 +/- 13 years old, with a mean duration on hemodialysis 42 +/- 44 months. The following measurements were recorded: predialysis mean arterial pressure (pre-MAP), post-dialysis MAP (post-MAP), percentage of change in MAP, pre-dialysis weight, post-dialysis weight, fluid removed by ultrafiltration during each dialysis session, interdialytic weight gain and excess weight over the desirable dry weight.Our results showed a hypertension prevalence of 59% (hypertension defined as pre-MAP +/- 110 mmHg). MAP was not different between men and women, and only 4.5% of patients had isolated systolic hypertension. All hypertensive patients were on treatment with antihypertensives. Reduction in post-MAP byor = 5% (controlled by ultrafiltration) was found in 68.5% of hypertensive and in 87.5% of normotensive patients. Age, primary renal disease, time on dialysis and adequacy of dialysis were not correlated with pre-MAP. Excess volume and interdialytic weight gain were found to correlate with pre-MAP (p = 0.03). Also, the weekly dosage of EPO had a significant correlation with pre-MAP (p = 0.03). No differences were found among four classes of antihypertensive drugs regarding the BP control. Patients with hypertension requiring one drug achieved a significantly (p0.05) lower pre-MAP than the group of patients receiving three or more drugs. In conclusion, hemodialysis population shows high prevalence of hypertension, resistant to antihypertensive treatment.Current methods of hemodialysis are not effective in controlling BP. This implies that more insight into the role of excess volume and vasomotor systems in the pathogenesis of dialysis hypertension is warranted.

The case of a 6-year-old boy with cytochrome oxidase (complex IV) deficiency and complete heart block, treated with permanent pacemaker implantation, is reported.

Pacing Clin Electrophysiol

Redox cycling compounds such as daunorubicin have been assumed to be toxic because they stimulate reactive oxygen-mediated lipid peroxidation. Furthermore, both DT-diaphorase and glutathione (GSH) have been regarded as protective cellular compounds against daunorubicin cardiotoxicity, but their role in daunorubicin nephrotoxicity remains unclear. To investigate this issue, 10 adult Wistar rats were twice injected with a single dose of 20 mg/kg body weight daunorubicin into the tail vein; the interval between injections was 48 h. A control group of 10 rats were injected with normal saline. One day after the second injection, all the animals were sacrificed and their kidneys were analyzed for malondialdehyde (MDA) as an index of lipid peroxidation, DT-diaphorase activity, and GSH and glutathione disulphide (GSSG) content. A significant increase of MDA concentration (2.41 vs. 1.64 p0.001) and DT-diaphorase activity (0.2 vs. 0.12, p0.001) was found in the renal tissue of daunorubicin injected rats. In contrast, GSH and GSSG levels were decreased in those animals (566 vs. 1282, p0.001 and 115 vs 187, p0.01, respectively). The results of this study give evidence that a high dosage of daunorubicin induces lipid peroxidation in renal tissue of rats stimulating the activation of DT-diaphorase and the detoxificative depletion of GSH.

Lipid peroxidation is a critical pathway of reactive oxygen species inducing tissue injury in postischemic acute renal failure. In order to evaluate the effect of renal ischemia reperfusion on kidneys, renal tissue malondialdehyde (MDA, nmol/g wet weight) concentration was measured in 29 male Wistar rats subjected to a midline abdominal incision and 60 min occlusion of the left renal artery. A right nephrectomy was performed at the beginning of the ischemic period. The animals were separated in four groups. Groups 1 (n = 7) and 3 (n = 7) underwent 60 min of ischemia and 15 min of reperfusion, respectively. Groups 2 (n = 8) and 4 (n = 7) were subjected to the same procedure but, in addition, they received 2.5 mg/kg TMZ into the tail vein 2 h prior to the left renal artery occlusion. A significant elevation of MDA after 60 min of ischemia (1.43 vs. 2.1, p < 0.001), which was augmented after 15 min of reperfusion (1.4 vs. 3.72, p < 0.001) was observed. Furthermore, there was a significant reduction of renal tissue MDA in ischemic rats treated with TMZ (group 3) (2.1 vs. 1.52, p < 0.001). The maximum reduction of renal tissue MDA was observed in ischemic-reperfused rats (group 4) that had received TMZ (3.72 vs. 1.36, p < 0.001). It is suggested that lipid peroxidation is a critical event in postischemic acute renal failure, and TMZ is a useful protective agent of renal damage from oxygen free radicals.

Clinical studies of treatment with angiotensin converting enzyme (ACE) inhibitors in patients with glomerular disease have shown the clinical efficacy of these agents. Fifteen renal transplant hypertensive and proteinuric patients on triple drug treatment with cyclosporin (CSA), azathioprine and methylprednisolone entered the therapeutic protocol of this study. All patients followed up last year had stable graft function (serum creatinine less than 2 mg/dl). Hypertension was treated by nifedipine retard and occasionally by furosemide. Patients with a renal artery graft stenosis, at least as judged by technetium-scan imaging were excluded. In order to evaluate the possible role of ACE inhibitors on hypertension and proteinuria, perindopril 4 mg/daily was added for two months to the above regimen. Two patients, who showed a reversible deterioration of renal function during treatment and three who did not comply to the therapeutic protocol were excluded. Systolic and diastolic blood pressure as well as 24 h urine protein was found to be significantly (p0.01) reduced at the end of the two-month combined treatment with perindopril and nifedipine retard in comparison to the result of monotherapy with nifedipine retard. GFR and ERPF showed no significant difference (NS) between the two modes of treatment. It is suggested that the combined treatment with nifedipine retard and perindopril is more effective than the monotherapy with nifedipine retard in the management of moderate to severe post-transplant hypertension and proteinuria of renal transplant patients.

The platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to blood PAF levels, serum PAF-acetylhydrolase (PAF-AH) activity and to their lipidoemic profile, was studied in 44 patients with coronary artery disease undergoing exercise tests. The PAF EC50 values in 21 patients with positive exercise test results were found to be significantly decreased at rest compared with 21 normal subjects (126±3⋅9 n M and 24⋅9±11⋅7 n M respectively) ( P

Erythrocytosis occurs in 10-15% of renal transplant recipients and there is evidence that the production of erythropoietin is modulated by adenosine. We prospectively evaluated the effects of theophylline, a nonselective adenosine antagonist, in 8 patients with erythrocytosis after renal transplantation. All patients were given triple-drug immunosuppressive therapy with methylprednisolone (8 mg/daily), azathioprine (2 mg/kg b.w. daily) and cyclosporin A (4 mg/kg b.w. daily). After an 8-week course of theophylline treatment (Theodur 300 mg x 2 daily), the mean serum erythropoietin levels were significantly reduced (from 61 mIU/ml before to 16.5 mIU/ml after treatment, p0.05). Also the hematocrit was reduced from 0.58 before to 0.50 after treatment (p0.05). The previous requirement of monthly phlebotomy was eliminated in all transplant recipients. The above effects were reproducible when the patients were rechallenged with theophylline after a recovery period. It is suggested that theophylline modulates the production of erythropoietin as well as the hematocrit levels in patients with erythrocytosis after renal transplantation and may be useful in the treatment of this condition.

Since immunosuppressed patients are at higher risk of serious influenza virus infection than healthy subjects, we decided to study the serological effectiveness of influenza vaccination on renal transplant patients, despite the theoretical aspect that such treatment could induce glomerular lesions through an immunological process. Forty transplant patients aged from 20 to 50 years with well functioning renal graft and no febrile episode were studied. Blood samples were collected before the intramuscular injection of 0.5 ml of multivalent influenza vaccine (PASTEUR MERIEUX SERUM VACCINS), at one and at two months after the vaccination. Before vaccination, the antibody titers to influenza virus ranged from 0 to 1/20 and after vaccination from 1/20 to 1/320. One month after vaccination 17/40 (42.5%), 18/31 (58%) and 16/33 (48%) patients showed a four-fold or greater increase of serum influenza antibody titers to antigens A/H3N2, A/H1N1 and B, respectively. A similar response at two months in relation to the first month response rate after vaccination was found in 15/17 (88%), 18/18 (100%), and 15/16 (93%) of transplant patients for the above mentioned three antigens. Side-effects were observed in two of the studied patients. Serum creatinine and urine protein were not changed. Also acute graft rejection episodes were not observed. It is suggested that influenza vaccination is safe and serologically effective on renal transplant patients.

As urinary tract infections in immunosuppressed renal transplant patients present a major therapeutic problem for clinicians in charge of renal units, the efficacy of the antibiotic ciprofloxacin in such cases was tested in this study. Twenty-six patients, 16 women and 10 men, aged 20 to 56 years, who developed urinary tract infection (UTI) from 6 months to 10 years after renal transplantation were included in the study. Of these patients, 20 (77%) showed cystitis and/or prostatitis and 6 (23%) clinical symptomatology of acute or recurrent pyelonephritis. Patients with obstructive uropathy were excluded. Urine culture was positive for E. coli in 16/26 patients (61.5%) and for proteus mirabilis, klebsiella, staphylococcus aureus in 10/26 (38.5%). All patients were given ciprofloxacin 250 mg x 2 daily for 10 days and the results of the treatment were compared to those of 60 nontransplant patients (controls) with UTI. Fourteen patients (54%) were completely cured and 10(38%) showed improvement, while the respective results in the controls were 68% (41/60) and 28%. Relapses occurred in two patients, one in each group. Serious side effects were not observed. It is concluded that ciprofloxacin is an effective and safe drug for the treatment of UTI in renal transplant patients.

Attention has recently been drawn to a severe form of hemorrhagic fever with renal syndrome (HFRS) found in the Balkan region of Europe. This disease is characterized by fever, abdominal or back pain, conjunctival injection, renal insufficiency, and a significant mortality rate (currently estimated to be approx. 14% in Greece. The disease resembles Korean hemorrhagic fever (KHF) of Korea and epidemic hemorrhagic fever (EHF) of China, rather than the milder nephropathia epidemica (NE) of Scandinavia and Western Europe. Patients who have recovered from this disease possess antibodies that react to highest titers with Hantaan virus, the cause of KHF and EHF, rather than with Puumala or Seoul viruses, the other known causes of HFRS. We have previously suggested, based on serological and epidemiological studies, that the disease found in Greece may be caused by a virus closely related or identical to the prototype Hantaan virus. In this communication, we report the isolation of a hantavirus from the urine of a severely ill patient with HFRS who was infected in northern Greece and the preliminary serological evidence to suggest that this virus represents a unique strain of hantavirus that is closely related to the prototype Hantaan virus.

The study is a comparison of 4 successive hemodialysis (HD) sessions on each patient, 2 with cuprophan (CU) membrane (Gambro 120 M) and 2 with Cellulose acetate (CA) (Cordis Dow 3500). 60 minutes prior to the HD session placebo or Ticlopidine (500 mg) was administered orally to each patient. Leucocyte and platelet counts, serum C3 complement, arterial PO2, PCO2 and PH were measured before and 15, 30, 60, 120 and 240 minutes after the beginning of HD. Leucocyte count fell markedly within 15 minutes of both placebo HD sessions, but it was significantly lower (p less than 0.005) in CA than CU membrane. Ticlopidine prevented significantly (p less than 0.01) the HD-induced leucopenia. Slight changes in platelet count, either in placebo or Ticlopidine study were observed. Serum C3 complement increased significantly (p less than 0.05) at 15 minutes of CU placebo session and was also correlated (p less than 0.01) with the concurrent leucopenia. The arterial PO2 decreased 22% and 13.5% during HD with CU and CA membranes respectively, but it was preserved within normal limits by Ticlopidine. The arterial PH was increased up to 7.4 at the end of all HD sessions, while PCO2 showed only slight changes. We conclude that: 1) CA membrane is better tolerated than CU 2) HD-induced leucopenia and hypoxemia are prevented by Ticlopidine, probably by modulating the complement activation.

Twelve patients, 8 male and 4 female, aged from 26 to 70 years were studied. They were on hemodialysis (HD) 4 h three times weekly with cuprophan hollow fiber dialyzers (Gambro 120M) and dialysate containing 35 mEq/L of acetate. The study compares two random HD sessions on each patient. Sixty minutes prior to one random session a placebo was administered orally, and prior to another random session piracetam was given at a dose of 8 g. Heparin dosage was not reduced during HD using QB 200 ml, QD 500 ml, and no ultrafiltration. Blood samples for leukocyte and platelet counts, serum C3, arterial paO2 and paCO2, thromboxane-B2 (TxB2), and β-thromboglobulin (β-TG) were taken from the arterial line before and at 15, 60, and 240 min during HD. Leu-kopenia at 15 min of HD was found to be less severe (p < 0.01) in the piracetam study than in the placebo, whereas platelet count did not change. Serum C3 was slightly increased in both studies. Arterial oxygen was preserved close to the initial levels by piracetam (91.66 mm Hg versus 81.08, p < 0.01 at 60 min, and 93.08 versus 80.17 mm Hg, p < 0.01 at 240 min of HD sessions) but paCO2 did not change significantly. TxB2 increased less with piracetam in comparison to placebo (p < 0.01 or p < 0.001), but (J-TG was reduced significantly by piracetam at any time during HD (p < 0.001). The above statistical analysis was done by paired t-test. Using the ANOVA test, significance was found only in plasma TxB2 levels between the two groups (p < 0.001). It is suggested that piracetam is a potent inhibitor of some HD-associated bioincompat-ibility parameters.

Deposition of C3 without immunoglobulins ("isolated C3") was found in 9.8% of 540 renal biopsies performed between 1976 and 1982. Thirty-two of these samples were from patients with systemic diseases (16), well defined forms of glomerulonephritis (9), other renal diseases (4) or renal allografts (4). The remaining 22 patients are described. Five had nephrotic syndrome, three of them with minimal changes on light microscopy and good response to corticosteroids. We were left with a group of 17 patients who presented with gross (4) or microscopic (12) hematuria or asymptomatic proteinuria (1) whose biopsies showed mesangial proliferation or/and hyperplasia and who followed a benign course over the mean 3 years of follow-up, with the exception of one whose renal function is declining. This clinicopathological picture is similar to that described in two previous publications suggesting that "Isolated C3 mesangial proliferative nephritis" is a recognizable sub-group within the spectrum of glomerulonephritis.

The study is a comparison of two successive HD sessions on each patient. 60 min prior to the first session a placebo was administered orally, while to the second session 500 mg ticlopidine. Arterial blood samples for leucocyte and platelet counts, C3 complement, blood gases, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) measurement were taken before and 15, 30, 60, 120, 240 min during each HD session. Platelet aggregation (ADP 1 microM/ml) was also carried out pre and post-dialysis. It is suggested that ticlopidine: 1) prevents HD-induced complement activation and related phenomena, 2) normalize the increased plasma levels of platelet markers 3) inhibits the ADP-induced platelet aggregation.