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Introduction/Objective. Thrombosis of hemodialysis catheters is one of the major complications, which leads to catheter dysfunction. Although tissue plasminogen activator has been proven to be effective in reestablishing blood flow rate through dysfunctional catheters, clinical data in Serbia are missing. The objective of the study was to analyze tissue plasminogen activator efficacy in reestablishing blood flow rate and the influence on catheter survival. Methods. The study included 53 tunneled catheters from 32 patients on hemodialysis. After catheter dysfunction was established, 580,000 units of tissue plasminogen activator was applied into each catheter lumen for about two hours before hemodialysis. The criteria for success was blood flow rate on the next hemodialysis ? over 200 mL/minute was considered to be complete success, 180?200 mL/minute partial success, and under 180 mL/minute was considered a failure. Results. Out of 53, 25 catheters (47%) had dysfunction with an incidence of 3.8/1,000 catheter days. Catheters placed in femoral veins, ?after-first? catheters, catheters with infection, and catheters in older patients had higher risk for dysfunction. Multivariate logistic regression analysis confirmed that only older age was significantly related to catheter dysfunction. Of the total of 50 applications of tissue plasminogen activator, 35 (70%) were successful, seven procedures (14%) were partially successful and eight (16%) dysfunctional catheters failed to respond to therapy. Six-, 12- and 24-month survival was 87%, 81%, and 20%, respectively, for catheters without dysfunction, and 71%, 47.5%, and 12%, respectively, for catheters with dysfunction. Conclusion. Tissue plasminogen activator dosing is noninvasive, efficient, and safe in reestablishing blood flow rate through dysfunctional catheters, thus prolonging catheters life and sparing patients from additional vascular procedures.

Background and Aims Home hemodialysis (HOHD) has been available as a modality of renal replacement therapy since the 1960s, in our center since 1972. Despite better patients’ outcome provided by HOHD comparing to hospital hemodialysis (HHD), its adoption has been limited worldwide. The aim of this study was to compare anemia, nutrition, mineral metabolism and morbidity in patients on HOHD and HHD. Method we analyzed dialysis and uremia related complications and morbidity in 19 HOHD patients in comparison with patients on HHD (N= 57). Each HOHD patient was previously matched with three patients on HHD by sex, age and reason for end stage renal disease (ESRD). Patients on HHD were on dialysis 3x4 h per week while patients on HOHD had dialysis on consecutive days in duration of 5-6 hours. Also, patients on HOHD were more frequent on hemodiafiltration (HDF), 89.5% of them, as compared to HHD patients (only 21.4%). Results All patients on HOHD were using AVF as vascular access for HD, and most of the analyzed HHD patients (only 5.3% used AVG). As revealed by hemoglobin level (Hgb) patients on HOHD had significantly better anemia control than HHD patients (12±2.3 vs. 10.2±1g/dl, p=0.004), despite the lower ferritin level (94±117 vs. 256±175ng/ml, p=0,001) and less frequent use of erythropoietin-stimulating agents (ESA), (and only 31% on HOHD vs 80% patients on HHD, p=0,001). By analyzing patients that used ESA therapy, we revealed that HOHD patients had lower weekly dose of ESA (5333±3265 IU vs. 6068±4145 IU). The values of intact parathyroid hormone (iPTH), did not differ significantly between HOHD (311±419pg/ml ; min 5,25, max 1529) and HHD (233±212pg/ml; min 19,25, max 926), but higher percentage of patients in HOHD group underwent parathyroidectomy (63% vs. 3.5%). The average values of calcium, and phosphorus did not significantly differ between HOHD and HHD patients (2.4±0.3 vs. 2.3±0.2mmol/l; 1.5±0.5 vs. 1.6±0.5mmol/l, respectively). HOHD patients had significantly higher albumin level (43±4.5 vs. 40.6±4g/l, p=0,035). There was no difference in annual hospital admission rate (0.4±0.5 vs. 0.6±0.7, p=0.35) between groups, but HHD patients had longer in-hospital stay. (4.8±5.3 days for HOHD vs. 7.3±9.3 days for HHD; p=0.16). Vascular access complications were most frequent reason for hospitalization in both groups (37%), followed by cardiovascular complications 13.6%, in HOHD group and infectious complications in HHD group 24%. Conclusion Our study has shown that HOHD provides some advantages over HHD including better quality of life and better anemia and nutrition control, better control of parathyroid function and shorter in-hospital stay. More frequent and longer dialysis sessions may be possible reason including HDF.

For adequate hemodialysis, functional vascular access is obligatory. Neointimal hyperplasia (NIH) has a central role in stenosis and thrombosis development, which represent the most frequent causes of vascular access failure. Polymorphism of different genes that have a significant role in endothelial function may have an impact on NIH development. Therefore, the aim of our study is to determine the effect of angiotensin-converting enzyme (ACE) I/D and matrix metalloproteinase-3 (MMP3) 5A/6A polymorphism on risk for developing vascular access failure in hemodialysis patients. The study included 200 patients on regular hemodialysis at Nephrology Department, University Medical Center Zvezdara. Retrospective analysis included a collection of general and vascular access data from medical records. Genetic analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Patients were divided into two groups: Group 1-patients who have never experienced vascular access failure and Group 2-patients who have at least one spontaneous vascular access failure. There was no difference in age, gender, hemodialysis vintage, main diagnosis, presence of hypertension, and diabetes mellitus between the two groups. There were no statistically significant differences in the frequencies of ACE and MMP3 genotypes between the two groups. Without statistical significance, it was found that homozygotes for I allele had two times higher risk for developing vascular access failure than homozygotes for D allele (OR 2.00; 95%CI: 0.727-5.503; P = 0.180). In addition, patients with 5A allele have 1.7 times higher risk for developing vascular access failure compared with patients without this allele (OR 1.745; 95% CI: 0.868-3.507; P = 0.118). Patients with vascular access failure do not have different genotype distribution regarding ACE gene and MMP3 gene polymorphism as compared with patients without vascular access failure. Still, homozygotes for I allele and homozygotes for 5A allele have higher risk for developing vascular access failure compared with other patients.

Introduction. Retrospective studies showed that hemodiafiltration was associated with a reduced risk of mortality compared with standard hemodialysis in the patients with end-stage renal disease. Recently, a few prospective randomized clinical trials found no advantage in survival with hemodiafiltration as compared with high-flux hemodialysis and low-flux hemodialysis. The aim of this study was to compare the parameters of hemodialysis adequacy and two-year survival of patients depending on the modality of hemodialysis. Material and Methods. A total of 159 hemodialysis patients were divided into 3 groups according to the type of hemodialysis treatment: group A - lowflux hemodialysis, group B - high-flux hemodialysis, and group C - hemodiafiltration. All patients had the same duration of hemodialysis sessions. The analysis included average one-year biochemical parameters, and two-year survival of patients. Results. The patients on hemodiafiltration were significantly younger, they had longer dialysis vintage and higher index of dialysis adequancy as compared with the patients on low-flux hemodialysis and high-flux hemodialysis, but without a difference between the two latter groups. Compared to the patients on low-flux hemodialysis, the patients on hemodiafiltration and high-flux hemodialysis had significantly higher hemoglobin value with less frequent erythropoietin stimulating agent use. According to Kaplan-Meier survival analysis, the patients on hemodiafiltration and high-flux hemodialysis had significantly better two-year survival than the patients on low-flux hemodialysis. Cox proportional hazards model confirmed that high-flux hemodialysis caused a significantly lower relative risk of mortality (56% reduction) compared to low-flux hemodialysis (hazard ratio 0.44; P=0.026), and hemodiafiltration caused a 58% reduction in the relative risk of mortality compared to low-flux dialysis (hazard ratio 0.42; P=0.105), but without a statistical significance. Conclusion. This study has demonstrated two-year survival benefit with high-flux hemodialysis and hemodiafiltration compared with low-flux hemodialysis. There was no difference in survival between high-flux hemodialysis and hemodiafiltration groups.

Background/Aims: Vascular calcifications are frequently found among dialysis patients, and the calcification process may influence the patient's outcome. The aim of the present study was to determine the role that vascular calcifications may have on autologous arteriovenous fistula (AVF) survival. Methods: This study included 90 patients (49 males, mean age 62 ± 11) with a native AVF treated by chronic hemodialysis (HD) for more than one year. The overall vascular calcification scores ranged from 0-11 (Adragao score + vascular access calcification score); patients were categorized into mild (score 0-3; n = 36), moderate (score 4-7; n = 24) and severe (score 8-11; n = 30) calcification groups. AVF survival was then followed for 5 years after calcification measurement or until the patient's death/transplantation. Results: Patients with more pronounced vascular calcifications were more frequently diabetic and male. Multiple linear regression analysis showed a significant relationship between calcification score and male gender, diabetes mellitus, previous duration of AVF, low dialysis flow rate and intact parathormone (iPTH) values. After multivariate adjustment for basal differences, Cox proportional analysis revealed a graded impact of calcification scores on AVF failure: moderate scores (were associated with a hazard rate (HR) of 3.82 (95% confidence interval (CI) 1.10-13.23) and severe scores with an HR of 4.65 (CI 0.97-22.38). Conclusion: Vascular calcifications are associated with worse survival of native arteriovenous hemodialysis fistulas.

Cardiovascular morbidity is the leading cause of death in dialysis patients and many risk factors have been involved in its pathogenesis. Genetic susceptibility may be of importance including polymorphism for matrix metalloproteinase 3 (MMP3), which is an enzyme that catalyzes the degradation of collagen, proteoglycans, fibronectin, laminine and elastin. The MMP3 gene promoter contains an insertion/deletion polymorphism characterised by an array of 5 or 6 adenosine residues (5A/6A) at -1612 position. Literature data show that the 5A or 6A allele of the MMP3 gene shows different risk for cardiovascular and overall outcome in general population. The aim was to analyze the -1612 5A/6A promoter polymorphism in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity and 7-year all-cause and cardiovascular mortality. This study included 196 patients on hemodialysis for longer than six months at University Medical Center Zvezdara. The leading causes of end stage renal disease were hypertension and diabetes mellitus. Venous blood was collected on midweek dialysis session and genotype analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method. Among the 198 hemodialysis patients, there were 142 (72%) 5A/6A heterozygotes, 12 (6%) 5A/5A homozygotes, and 44 (22%) 6A/6A homozygotes. These data are consistent with Hardy-Weinberg equilibrium. After 7-year follow-up, the 5A homozygotes showed the lowest all-cause and cardiovascular survival, while the 6A homozygotes showed the highest cardiovascular survival. The 5A allele of the MMP3-gene promoter polymorphism is a potential risk factor in the poor outcome of hemodialysis patients.

Introduction. Cardiovascular morbidity and mortality are the major concern in dialysis patients and many risk factors are thought to be involved in its pathogenesis. Apart from traditional and non-traditional risk factors, the genetic susceptibility may be of importance, including renin-angiotensin system gene polymorphism. The aim of this study was to analyse renin-angiotensin system polymorphism in our group of hemodialysis patients and to correlate the findings with cardiovascular morbidity. Material and Methods. The study included 196 patients on regular hemodialysis on polysulphone membrane three times per week for more than six months. Genetic analysis was performed by using polymerase chain reaction - restriction fragment length polymorphism method. Results. Out of 196 patients, 55% had I/D genotype, 35% had D/D and 10% had I/I, including angiotensin-converting enzyme polymorphism. It was shown that the patients with D allele genotype developed a significantly higher incidence of left ventricular hypertrophy and peripheral vascular disease. The angiotensin-converting enzyme polymorphism showed a significant association with the incidence of cerebrovascular accident and hyperlipoproteinemia in our group of hemodialysis patients. Conclusion. The angiotensin-converting enzyme gene polymorphism is associated with the development of cerebrovascular accidents and hyperlipoproteinemia. Allele D of this gene increases the risk for the development of left ventricular hypertrophy and peripheral vascular disease significantly in hemodialysis patients. A longer follow-up is needed to make the definitive conclusion about the influence of angiotensin-converting enzyme polymorphism on cardiovascular morbidity and its importance in everyday clinical practice.

Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The impact of vascular calcification process on AVF survival remains unclear and results of several studies about this issue are controversial. In the light of the new knowledge about the different susceptibility for calcification process in different blood vessels, the aim of our study was to analyze whether the calcification of AVF-blood vessels may have an impact on AVF longevity. The study included 90 patients, 49 males and 41 females, all of them Caucasians, with a mean age 62 ± 11 years, on regular hemodialysis for more than 1 year with patent primary AVFs. Vascular calcification in AVF-blood vessels or in the anastomotic region was detected using X-ray examination. Calcification in AVF-blood vessels was found in 62% of patients. Binary logistic regression analysis demonstrated that male gender, presence of diabetes mellitus and longer duration of AVF before calcification determination were associated with calcification of AVF-blood vessels. Using a Cox proportional hazard model adjusted for these standardized predicted values revealed that patients with present AVF-blood vessels calcification had increased risk to develop AVF failure with a hazard rate of 3.42 (95% confidence interval 1.00–11.67; P = 0.049). Calcifications of AVF-blood vessels are found frequently among dialysis patients and may jeopardize the survival of native AVF. We suggested the local X-ray as simple and valid method for detection of patients that are at risk for AVFs failure which should be monitored more closely.

Uremia-related inflammation is prone to be a key factor to explain high cardiovascular morbidity in hemodialysis patients. Genetic susceptibility may be of importance, including IL-10, IL-6, and TNF. The aim was to analyze IL-10, IL-6, and TNF gene polymorphisms in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity. This study included 169 patients on regular hemodialysis at Zvezdara University Medical Center. Gene polymorphisms for IL-10, IL-6 and TNF were determined using PCR. These findings were correlated with the cardiovascular morbidity data from patient histories. Heterozygots for IL-10 gene showed significantly lower incidence of cardiovascular events (p = 0.05) and twice lower risk for development of myocardial infarction, but experienced twice higher risk for left ventricular hypertrophy. Regarding TNF gene polymorphism, patients with A allele had 1.5-fold higher risk for cerebrovascular accident and cardiovascular events and 2-fold higher risk for hypertension and peripheral vascular disease. Patients with G allele of IL-6 gene experienced 1.5-fold higher risks for cerebrovascular accident. We need studies with larger number of patients for definitive conclusion about the influence of gene polymorphisms on cardiovascular morbidity in hemodialysis patients and its importance in everyday clinical practice.

Purpose Intra-dialytic morbid events (IME; e.g. hypotension, cramps, headaches) are frequent complications during hemodialysis (HD), known to be associated with ultrafiltration-induced hypovolemia and body temperature changes. Feedback control of blood volume adjusts the ultrafiltration rate in order to keep the blood volume above the patient's individual limit; feedback control of blood temperature maintains the mean arterial blood temperature at the individual pre-dialytic level. Each of these methods reduces the frequency of IME. Methods In a randomized clinical trial the simultaneous application of both feedback controls was investigated for the first time. In 15 weeks, each patient went through 3 study phases: an observational screening phase, a standard phase (STD), and a blood temperature- and blood volume-control phase (CTL). Patients with at least 5 sessions with IME out of 15 sessions in the screening phase were eligible for the study and randomized either into sequence STD-CTL or CTL-STD. Results 26 patients completed the study according to protocol, and 778 HD treatments were analyzed. The general treatment parameters were similar in both study phases: treatment duration (STD: 244 min, CTL: 243 min, NS), pre-dialytic weight (STD: 72.3 kg, CTL: 72.2 kg, NS), and weight loss due to ultrafiltration (STD: 3.26 kg, CTL: 3.15 kg, NS). The proportion of HD treatments with IME was 32.8% during STD and 18.0% during CTL (p=0.024). Conclusions The frequency of HD sessions with IME was significantly reduced by 45% compared to standard HD in this randomized clinical trial by use of individualized HD treatments with simultaneous feedback control of blood volume and blood temperature.

Background/Aims: Compared to all other complications, literature data about vascular access aneurysm (VAA) are the scarcest. The aim of this cross-sectional study was to evaluate the prevalence of arteriovenous fistula (AVF) aneurysms and to confirm the risk factors for their appearance. Methods: The presence, number and morphological characteristics of AVF aneurysms were confirmed, and according to the score of AVF aneurysm (the sum of the length and width in cm), patients were classified into group 1 (score ≤12) and group 2 (score >12). Analysis included the last data from the medical records including vascular calcifications score. Results: Out of 181 patients, 150 with native fistula were included in this study. Aneurysmatic changes were detected in 90 (60%) patients, and the majority had two or more aneurysms. VAA were more frequent in patients with adult polycystic kidney disease (ADPKD) than in other diagnostic categories. By using forward stepwise logistic regression, we confirmed that patients on high-flux hemodialysis (HD) had 5.3-fold higher risk, and patients with diabetes mellitus had 5.8-fold less risk for developing AVF aneurysm. While vascular calcification score did not influence the incidence of VAA, higher PWV had significant negative influence on formation of AVF aneurysm (OR 1.25, 95% CI 1.003-1.56, p = 0.047). By ROC curve analysis, it was determined that patients who were longer than 5.7 years on HD had greater risk for developing VAA (area = 0.741, p = 0.000). Conclusion: This single-center study confirmed the very high prevalence of VAA (60%). Aneurysms were more frequent in patients with ADPKD and in those who had longer dialysis vintage on high-flux membranes with higher blood flow rate.

Introduction. Hypertension is evident in 80%-85% of patients with chronic renal failure and antihypertensive therapy is needed in 25%-30% of patients. Apart from antihypertensive effect, ACEi?s decrease the left ventricular hypertrophy and mortality in dialysis patients. Even so, their use is limited due to hyperkalemia. Objective. The objective of the study was to compare the effect of fosinopril and enalapril on serum potassium level in hypertensive hemodialysis patients. Method. Prospective pilot study included 16 patients undergoing chronic hemodialysis, with mean age of 58.9?9.6 years and mean duration of hypertension 11.3?7.1 years. The effect of antihypertensive drugs of equivalent dose was followed during three periods (three months each): period 1 (therapy with enalapril), period 2 (therapy with fosinopril) and period 3 (therapy with enalapril). Dialysis conditions were constant and patients were without signs of catabolic state. Laboratory results were followed on monthly basis and mean values were compared by ANOVA-one way test. Difference between variables between periods was tested using Bonferoni method. Results. There was significant difference between mean serum potassium levels throughout three therapeutic periods (5.88?0.38 vs. 4.99?0.44 vs. 5.46?0.46mmol/l; p