Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients

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

Endothelial dysfunction and oxidative stress in chronic renal failure

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.     

High prevalence of colon adenomas in end‐stage kidney disease patients on hemodialysis undergoing renal transplant evaluation

The aim of this study was to determine whether patients with end‐stage kidney disease (ESKD) on hemodialysis (HD) undergoing kidney transplant evaluation are at higher risk for colonic neoplasia than the general population. This is a retrospective cohort study of patients with ESKD who underwent a first screening colonoscopy while undergoing kidney transplant evaluation. Data were collected on the prevalence of adenomatous polyps and advanced adenomas in 70 patients with ESKD and 70 controls, undergoing their first screening colonoscopy, matched for age, gender, and endoscopist. At the time of the colonoscopy, an average time on HD was 3.2 ± 2.9 yr. The prevalence of adenomatous polyps was significantly higher in ESKD on HD (54.3% vs. 32.9%, p = 0.008) than in controls. In a multivariate analysis controlling for other factors, ESKD on HD remained a risk factor for the presence of adenomas (OR 3.06, 95% CI 1.21, 7.73). No colonoscopy‐related complications were reported in the patients with ESKD on HD. We demonstrate a significantly higher prevalence of adenomatous polyps in patients with ESKD undergoing a first screening colonoscopy as part of kidney transplant evaluation. In addition, colonoscopy can be safely performed in this population.     

The role of intrinsic fibrinolytic system activation in pathogenesis of hemostasis disturbances in hemodialyzed patients with chronic renal failure

In the hemodialysis patient, hemostasis changes may occur. The contribution of fibrinolysis in pathogenesis of these disorders is unclear. The aim of the study was to estimate intrinsic fibrinolysis pathway in patients treated with hemodialysis (HD) because of chronic renal failure caused by chronic glomerulonephritis. The study was performed with 43 patients; the control group consisted of 51 healthy volunteers chosen by sex and age. The following parameters were determined: concentration of the urokinase plasminogen activator antigen (uPA:Ag), plasmin--antiplasmin complexes (PAP), fibrin and fibrinogen degradation products (FDP), activity of prekallikrein (PK) and C1-inhibitor (C1-INH) and also euglobulin clot lysis time (ELT). The above parameters were assessed in the patients before and after HD and were compared with the control group. In the HD patients, in comparison with the control group, prolonged statistically ELT [153 (125;215) vs. 105 (75;142) min.; p<0.001], with increase of PAP (508.6 +/- 274.7 vs. 184.7 +/- 69.4 microg/L; p<0.001) and FDP concentrations [5 (5;15) vs. 2.5 (0;0.3) microg/mL; p<0.05] before the procedure were determined. It suggests increased plasmin production and fibrin digestion despite determination of decreased general fibrinolytic activity. The C1-INH activity before HD was also significantly increased as compared with the control group [157 (136;171) vs. 107 (100;124)%; p<0.001], and its significant decreased after the HD is 157.7 +/- 23.9 vs. 122.3 +/- 20.3%; p<0.001, as it seems to be a nondirect proof of intrinsic pathway contribution in fibrinolysis activation in the HD patients. The remaining examined parameters did not change significantly after the dialysis procedure.     

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.     

Cellular immunity and levels of parathyroid hormone in uremic patients receiving hemodialysis

OBJECTIVE: The clinical relevance of altered lymphocyte function and the possible relation with uremic toxins, such as parathyroid hormone (PTH) is not well understood. We studied the changes in cellular immunity in patients in hemodialysis (HD) therapy and examined the relationship between T-lymphocyte function and plasma levels of PTH. PATIENTS AND METHODS: Thirty-four patients (14 male) were enrolled in this study (mean age: 63.20 +/- 10.01 years, M +/- SD, 12 h/week HD). Our study population was divided into two groups: 18 patients with increased levels of PTH and 16 patients with normal levels of PTH. Lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD19+, CD3-/16+56+, CD4/CD8 ratio) were quantitated in both groups using monoclonal antibodies (Immunotech, Coulter) and flow cytometric analysis. Following analysis of variance (ANOVA) testing was performed to test differences between groups (SPSS version 10). RESULTS: A significant increase of CD2 was noticed in patients with increased levels of PTH (84.8 +/- 5.5 vs. 79.8 +/- 4, p<0.05). The CD3 population was also increased in patients with elevated PTH (72 +/- 8.6 vs. 68 +/- 9.2, p=NS). This group of patients had also significantly increased levels of CD3/8 (44.8 +/- 9.8 vs. 37.1 +/- 5.8, p<0.05). The CD4/CD8 ratio levels were higher in patients with elevated PTH compared with those who had normal PTH (2.2 +/- 1.5 vs. 1.5 +/- 0.8, p=NS). CONCLUSIONS: The elevated level of PTH seems to affect the lymphocyte function and is associated with changes in cellular immunity in the hemodialysis population. Our study is in progress in order to enlarge our study population and collect more data, which will lead us to more solid conclusions.     

Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia.

The metabolic basis for the enhanced tolerance of immature hearts to ischemia remains to be elucidated. Loss of high-energy phosphate nucleotides occurs during ischemia/reperfusion in mature (adult) hearts through the breakdown of adenosine triphosphate, diphosphate, and monophosphate (nondiffusible) to adenosine (freely diffusible). However, previous work has shown that after ischemia nondiffusible nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The enzyme responsible for the conversion of adenosine monophosphate to adenosine is 5'-nucleotidase. We therefore hypothesized lower activity of this enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document 5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of 5'-nucleotidase activity with functional recovery from ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for 5'-nucleotidase by the linked formation of nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). 5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1) 5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after ischemia inversely relates to 5'-nucleotidase activity.     

Influence of parenteral iron therapy and oral vitamin E supplementation on neutrophil respiratory burst in chronic hemodialysis patients

BACKGROUND: Bioincompatibility of hemodialysis (HD) membranes is responsible for neutrophil activation leading to oxidative stress, which can be further increased by intravenous (IV) iron (Fe) administration. The aim of our study was to monitor neutrophil respiratory burst during HD and to find out whether this process is influenced by IV Fe and oral vitamin E administration. METHODS: Within four HD sessions, blood samples were taken from seven chronic HD patients at time 0 (before HD), 60, 70, and 130 min of HD session. Neutrophil respiratory burst was assessed by luminol-enhanced chemiluminescence (CL). Plasma advanced oxidation protein products (AOPP) concentration was measured spectrophotometrically. During the second and the fourth HD, 62.5 mg of sodium ferric gluconate was applied IV in the 65th minute of HD. Before the last two HD, the patients were given orally 200 mg of vitamin E daily for 7 days. Patient's results were compared with healthy controls. RESULTS: Predialysis CL is higher in patients than in controls (1,926 +/- 436 vs. 1,083 +/- 325 RLU, p<.01). CL decreases in the 60th min of HD (1,926 +/- 436 vs. 1,220 +/- 599 RLU, p<.05); thereafter, it remains stable. After Fe application, CL increases at time 130 compared with CL at time 60 (1,303 +/- 269 vs. 877 +/- 292 RLU, p<.05). AOPP concentration is higher in patients than in controls (137.5 +/- 42.7 vs. 88.9 +/- 24.8 micromol/L, p<.01) and remains unaffected by vitamin E supplementation. After vitamin E intake, predialysis CL remains significantly higher than in controls, and changes in CL during HD are minimal despite Fe administration. CONCLUSION: HD patients' neutrophils generate more oxygen radicals than in healthy individuals. This production decreases during HD and then increases after IV Fe administration. Short-term vitamin E administration attenuates this fluctuation of neutrophil oxidative metabolism, without affecting the total degree of oxidative stress.     

Hemodialysis Treatment in Patients with Balkan Endemic Nephropathy: An Epidemiological Study

Aim. To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. Methods. A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. Results. Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004–2006) The mean survival time of BEN males was 4.70 (95% CI 3.66–5.75) and for females was 5.02 (95% CI 1.47–4.53). Difference between males and females was not statistically significant (log rank 0.14, p?=?0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97–5.70) in BEN patients and 3.1 (95% CI 2.78–3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p?=?0.0038, P < 0.01). Conclusion. The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Oxidative stress markers in hepatitis C infected hemodialysis patients

BACKGROUND: Oxidative stress in hemodialysis (HD) patients or hepatitis C virus (HCV) infections may be related to increased production of free radicals. We assessed the effect of HCV infection on the oxidative stress markers, malondialdehyde (as TBARS), protein carbonyl content and protein sulfhydryl groups, in chronic HD patients. METHODS: Twenty HCV infected patients (9 men and 11 women, age 44.8 +/- 14.3 years) and 10 non-HCV infected patients (6 men and 4 women, age 55.6 +/- 14.3 years) receiving regular HD were recruited. The average hemodialysis duration was 30 +/- 8 months for HCV (+) patients and 14 +/- 8 months for HCV (-) patients. Controls consisted of healthy subjects. RESULTS: Serum TBARS and carbonyl content were significantly elevated in HCV(-) patients (p<0.001, p<0.05) and in HCV(+) patients (p<0.001, p<0.001) vs. Controls. There was also a significant difference in serum TBARS and carbonyl content between HCV(-) patients and HCV(+) patients (p<0.001, p<0.05). Serum protein sulfhydryl groups in HCV(-) and HCV(+) patients were the same, but significantly lower than in Controls (p<0.001, p<0.001). When HCV(+) patients were divided into two sub-groups, one with shorter (13.4 +/- 8 months; n=7) and the other with longer (40.3 +/- 8 months; n=13) duration of HD treatment, no differences were found between subgroups. CONCLUSION: HCV infection may aggravate oxidative stress in HD patients.     

Vascular calcification is not related to serum fetuin-A and osteopontin levels in hemodialysis patients

Introduction

Vascular calcification (VC) in hemodialysis (HD) patients is a sign of severe cardiovascular disease and can predict cardiovascular outcomes. Fetuin-A and osteopontin (OPN) inhibit VC. Serum fetuin-A levels are lower in patients with end-stage kidney disease (ESKD) and in those who are on chronic HD therapy. However, there are limited data concerning OPN in patients who are on dialysis. The aim of our study was to determine VC in HD patients, the relationship between VC and 25-OH-vitamin D, fetuin-A, and OPN levels, and independent predictors of VC.

Materials and methods

Ninety-three patients with ESKD on HD therapy were recruited. Among these patients, 44 were male and 49 were female. The patient group was compared with a group of 20 healthy controls of similar age and sex. A plain radiograph of the hand was taken using a mammography machine for the evaluation of VC. Serum fetuin-A, OPN, and 25-OH-vitamin D levels of both patients and controls were measured.

Results

VC was detected in 45 (48.4%) HD patients. When patients were compared with healthy controls, fetuin-A levels (p < 0.029) were significantly lower in patients, whereas OPN (p < 0.000) and VC (p < 0.002) were significantly higher in the patient group. Age [odds ratio (OR) 1.036], the presence of diabetes mellitus (DM) (OR 17.527), and high parathyroid hormone (PTH) levels (OR 1.002) were independent predictors of VC in a logistic regression model including the following factors: age, the presence of DM, HD duration, and serum albumin, phosphate, PTH, 25-OH-vitamin D, fetuin-A, OPN, and calcium levels. No significant correlation was found between patients with VC and patients without VC in terms of fetuin-A, OPN, and 25-OH-vitamin D levels.

Conclusions

VC is a frequent sign in patients undergoing HD and is not related to serum fetuin-A and osteopontin levels. Age, the presence of DM, and high PTH levels were independent predictors of VC in patients undergoing HD. Further studies are warranted to understand the mechanism underlying and the factors contributing to VC.

     

Prognosis and risk factors for cardiac valve calcification in Chinese end-stage kidney disease patients on combination therapy with hemodialysis and hemodiafiltration

BackgroundCardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration.MethodsWe conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography.ResultsESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification.ConclusionsCVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.     

Vascular calcification and cardiovascular function in chronic kidney disease.

BACKGROUND: Vascular calcification and arterial stiffening are independent predictors of all causes and cardiovascular mortality in chronic kidney disease (CKD). Few data are currently available comparing vascular calcification and its attendant functional cardiovascular consequences between CKD stage 4 patients and both peritoneal dialysis (PD) and haemodialysis (HD) (CKD stage 5) patients. METHOD: We studied 134 subjects (60 HD, 28 PD and 46 CKD 4). Vascular calcification was quantified using multi-slice spiral CT scanning of a 5 cm standardized segment of superficial femoral artery. Pulse wave analysis and pulse wave velocity were assessed using applanation tonometry, to determine arterial compliance. Further digital arterial pulse wave analysis was used to measure systemic haemodynamic variables. All medications were recorded and biochemical variables were time averaged for the 6 months prior to entering the study. RESULTS: Forty-seven percent of CKD 4 patients demonstrated vascular calcification as compared with CKD 5 (71% PD and 73% HD, P = 0.02). HD patients had higher calcification scores (median 121) than either PD (median 21) or CKD 4 (median 0) (P = 0.008). There were no significant differences in baseline characteristics between the groups. Comparing tertiles of patients (based on calcification score), increased calcification score was associated with a reduction in arterial compliance (mean PWV 8.9 +/- 1.1, 11 +/- 3.6, 11.3 +/- 3.7 m/s, P = 0.005). The degree of calcification did not influence systolic blood pressure (BP), diastolic BP or heart rate. However, more heavily calcified patients demonstrated significantly higher mean pulse pressures (58 +/- 19, 74 +/- 22 and 72 +/- 25 mmHg, P = 0.001), lower total peripheral resistance (1.5 +/- 1, 1.3 +/- 0.8, 0.9 +/- 0.4, P = 0.01) and higher stroke volume (84 +/- 25, 95 +/- 29, 106 +/- 39 ml, P = 0.01). More heavily calcified patients were significantly older and predominantly male. CONCLUSION: This study has successfully utilized a novel technique for the quantification of calcification. We have demonstrated vascular calcification and associated cardiovascular dysfunction in CKD 4, PD and HD with significant differences between the groups. Thirty percent of individuals show no calcification, even those established on renal replacement therapy for a prolonged period of time. Further work is required to identify factors which promote progression of arterial calcification in those who are susceptible.     

Treatment of refractory hyperparathyroidism in patients on hemodialysis by intermittent oral administration of 1,25(OH)2vitamin D3

Intermittent oral administration of high dose 1,25(OH)2vitamin D3 was conducted in 7 patients associated with treatment-resistant secondary hyperparathyroidism (2nd HPT) on hemodialysis (HD) therapy. Each patient had a long history of HD therapy (range: 101-181 months, 145 +/- 29 months). Although serum calcium levels were maintained under the upper limit of the normal range with the appropriate dose of 1 alpha(OH)vitamin D3 every day before the present therapy, 2nd HPT could not have been controlled. The dose of 2-3 micrograms of 1,25(OH)2vitamin D3 3 times a week could successfully suppress serum levels of parathyroid hormone (iPTH) in all 7 patients after 20-32 weeks. The vitamin was given in the evening before each HD session and the dose and frequency of administration were dependent of the serum calcium level in each patient. After 20 weeks the iPTH-C and iPTH-intact levels decreased significantly from 35.0 +/- 15.8 to 18.6 +/- 11.7 ng/ml and from 533.2 +/- 200.0 to 249.5 +/- 136.2 pg/ml, respectively. The frequency of harmful elevations of serum calcium levels was not significantly increased in comparison with that in the previous period of the study, because serum calcium levels were strictly monitored with frequent checks. In conclusion, we could safely obtain an effect similar to the intravenous administration of the vitamin through the intermittent administration of a high oral dose 1,25(OH)2vitamin D3 in the treatment of refractory 2nd HPT in patients on HD therapy.     

Young hemodialysis patients are exposed to hyperhomocysteinemia.

OBJECTIVE: Homocysteine is one of the cardiovascular risk factors in hemodialysis (HD) patients. Studies were performed to assess the effects of folic acid on pulse wave velocity (PWV) in HD patients. METHODS: In a cross-sectional study, plasma total homocysteine (tHcy) was measured in 49 patients on maintenance HD. Ten HD patients younger than 45 years old entered the prospective study. Monthly changes in PWV were compared before and during folic acid treatment. RESULTS: Younger HD patients had higher tHcy (r = -0.53, n = 49, P < .001). Patients who manifested myocardial ischemia (37 +/- 3 nmol/mL) possessed higher tHcy than those who did not (30 +/- 3 nmol/mL, P < .05). In prospective study, folic acid treatment (10 to 20 mg/d) failed to alter blood pressure and biochemical parameters, including lipids, calcium, phosphate, and parathormone. However, in association with a decrease in tHcy (46 +/- 5 to 27 +/- 3 nmol/mL, n = 10, P < .005), progressive increases in PWV (33 +/- 8 to 3 +/- 6 cm/sec/month, P < .01) were stopped. CONCLUSIONS: The present findings indicate that young HD patients are exposed to severe hyperhomocysteinemia, and suggest that relatively large doses of folic acid attenuate progressive increases in PWV of young or middle-age HD patients.     

Oral and parenteral essential amino acid therapy in malnourished hemodialysis patients

BACKGROUND/AIMS: Malnutrition has been encountered more frequently than expected and is associated with increased morbidity and mortality in hemodialysis (HD) patients. Until the last few years, only oral and enteral nutritional supplies have been used in the treatment of malnutrition in HD patients. However, intradialytic parenteral essential amino acid (EAA) nutrition has recently been introduced to treat these patients. The present study was conducted to compare both methods of EAA nutrition, oral and parenteral, in malnourished HD patients. METHODS: Half of the 20 malnourished HD patients in this study received 0.9 g/kg/week of oral EAA (oral group), while the other half of the patients were treated with the same dose of parenteral EAA (parenteral group) for 4 months. However, at the very beginning of the study, 4 patients from the oral group were transferred to the parenteral group because of complaints such as nausea and vomiting. Therefore, this study was completed with 6 patients in the oral group and 14 patients in the parenteral group. Some biochemical parameters, including blood lymphocyte counts and anthropometric measurements as indicators of the nutritional status, were obtained from both of the groups in the pre- and posttreatment periods. RESULTS: Following the treatment, there were no statistically significant differences between the groups with respect to anthropometric measurements. However, statistically significant increases were observed in serum albumin (p = 0.048) and creatinine (p = 0.006) levels and blood lymphocyte counts (p = 0.006) in the parenteral group, while there were statistically significant increases only in serum calcium (p = 0.028) levels and blood lymphocyte counts (p = 0.038) in the oral group following the treatment when compared to pretreatment values. CONCLUSION: These results show that parenteral EAA therapy is more comfortable and effective than oral EAA therapy in the treatment of malnourished HD patients.     

Diagnostic Value of the Aminopeptidase N,N-Acetyl-β-D-Glucosaminidase and Dipeptidylpeptidase IV in Evaluating Tubular Dysfunction in Patients with Glomerulopathies

Aim. The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-β-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. Subjects and Methods. PC-1, APN, NAGA, and DPP IV activities were determined in serum, urine, and lymphocytes of 178 subjects, including 10 patients with membranous nephropathy, 38 with IgA nephropathy, 29 with lupus nephritis, 51 with diabetic nephropathy, and 50 control subjects. Results. Urinary PC-1 excretion in IgA nephropathy group was significantly higher (p < 0.05) than in controls. Urinary NAGA excretion was markedly (p < 0.01) higher in membranous nephropathy group, and APN excretion in diabetic nephropathy group was significantly higher (p < 0.01) than in healthy controls. Urinary APN activity was significantly (p < 0.01) higher in both type 1 and type 2 diabetic patients with microalbuminuria, as well as urinary NAGA and DPP IV activities in type 2 diabetics with microalbuminuria (p < 0.01 and p < 0.05, respectively) compared to controls. Serum PC-1 and APN activities were significantly higher than the control level in membranous nephropathy group, as well as serum PC-1 and DPP IV activities in IgA nephropathy patients (p < 0.05). However, significantly lower serum DPP IV and APN activity was observed in type 2 diabetics with microalbuminuria compared to controls (p < 0.05). Conclusion. Damage of tubules in primary glomerulonephritis, lupus nephritis, and diabetic nephropathy is accompanied by a release of several tubular enzymes, with possible diagnostic and prognostic significance. Increased serum PC-1, APN, and DPP IV activities could be also of diagnostic significance.     

Acute effects of haemodialysis on endothelial function and large artery elasticity.

BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.     

Hemodialysis treatment in patients with Balkan endemic nephropathy: an epidemiological study

AIM: To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. METHODS: A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. RESULTS: Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004-2006) The mean survival time of BEN males was 4.70 (95% CI 3.66-5.75) and for females was 5.02 (95% CI 1.47-4.53). Difference between males and females was not statistically significant (log rank 0.14, p = 0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97-5.70) in BEN patients and 3.1 (95% CI 2.78-3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p = 0.0038, P < 0.01). CONCLUSION: The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Is adenosine preconditioning truly cardioprotective in coronary artery bypass surgery?

BACKGROUND: The large number of experimental studies showing that adenosine "turns on" the protein kinase C (PKC)-mediated pathway that accounts for the cardioprotection conferred by ischemic preconditioning contrasts with the scarcity of clinical data documenting the preconditioning-like protective effect of adenosine during cardiac operations on humans. METHODS: Forty-five patients undergoing coronary artery bypass were randomized to receive, after the onset of cardiopulmonary bypass, a 5-minute infusion of adenosine (140 microg x kg(-1) x min(-1)) followed by 10 minutes of washout before cardioplegic arrest (n = 23) or an equivalent period (15 minutes) of prearrest drug-free bypass (controls, n = 22). Outcome measurements included troponin I release over the first 48 postoperative hours and activity of ecto-5'-nucleotidase, an admitted reporter of PKC activation, as assessed on right atrial biopsies taken before bypass and at the end of the preconditioning protocol (or after 15 minutes of bypass in control patients). RESULTS: Aortic cross-clamping times were not different between the two groups. Likewise, prebypass values of ecto-5'-nucleotidase (nanomoles/mg protein per minute) were similar in control (3.14+/-1.02) and adenosine-treated (2.66+/-1.08) patients. They subsequently remained unchanged in control patients (3.87+/-1.65) whereas they significantly increased after adenosine preconditioning (4.47+/-1.96, p<0.001 versus base line values). However, peak postoperative values of troponin I (microg/L) were not significantly different between control (4.8+/-2.8) and adenosine-preconditioned patients (5.9+/-6.6) nor were the areas under the curve. There were no adverse effects related to adenosine. CONCLUSIONS: Adenosine, given at a clinically safe dose, can turn on the PKC-mediated signaling pathway involved in preconditioning but this biochemical event does not translate into reduced cell necrosis after coronary artery surgery, suggesting that a preconditioning-like protocol may not be the best suited for exploiting the otherwise well-documented cardioprotective effetcs of adenosine.