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Introduction: Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon. Methods: The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression. Results: Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing. Conclusion: In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.

BACKGROUND AND AIMS Many studies have shown that home haemodialysis (HOHD) provides fewer complications and better outcomes as compared with hospital haemodialysis (HHD). The aim of this study was to compare morbidity and survival in patients on HOHD and HHD. METHOD We analysed 26 prevalent HOHD patients who were matched with 52 HHD patients according to sex, age and Davies Comorbidity Index (DCI). DCI is based on seven groups of comorbidities: ischaemic heart disease (IHD), left ventricular dysfunction (LVD), peripheral vascular disease (PVD), malignancy, diabetes mellitus (DM), systemic collagen vascular disease and other significant pathology. Grade 0 had patients without any of these comorbidities, grade 1 those with 1–2 and those with 3 or more comorbidities had grade 2. Patients were followed from January 2011 to January 2020. We analysed an overall number of hospitalizations during the study period, a number of hospitalizations per year (annual hospital admission rate) and longevity of in-hospital stay (days). We categorized each hospitalization into 1 of 4 causes: cardiovascular disease (CVD), infection, vascular access dysfunction, or other cause. RESULTS Median age for HOHD and HHD patients was 55.7 and 56 years respectively and 77% of patients in both groups were men. Majority of the patients in both groups had DCI 1 (65%), 31% had DCI 0 and only 4% had DCI 2. The most common comorbidity for both HOHD and HHD patients was IHD (35% and 29% respectively), followed by HCV infection (35% and 17% respectively) and PVD (11.5% and 15% respectively). There was no difference between HOHD and HHD patients in an overall number of hospitalization (3.7 ± 3.3 versus 3.9 ± 2.8; P = .47), nor in annual admission rate for all-cause morbidity (0.5 ± 0.4 versus 0.6 ± 0.4; P = .28), but HHD patients had longer in-hospital stay (7.4 ± 9.8 days versus 9.3 ± 8.7 days; P = .05). Cause-specific morbidity showed that HHD patients had a more frequent annual admission rate for CVD (0.2 ± 0.1 versus 0.4 ± 0.3; P = .05), while there were no differences for infections (0.3 ± 0.2 versus 0.3 ± 0.3; P = .9) nor vascular access complications (0.3 ± 0.3 versus 0.4 ± 0.3; P = .3). Also, annual in-hospital stays for CVD (3.0 ± 3.1 versus 4.0 ± 4.5 days; P = .5), infection (6.4 ± 7.5 versus 5.7 ± 7.6 days; P = .6) and vascular access complications (6.0 ± 7.0 versus 7.7 ± 7.8 days; P = .5) did not differ between HOHD and HHD group. Kaplan–Meier curve revealed that survival in HOHD and HHD patients were 92.3% versus 90.4% at 3 years, 84.6% versus 70.2% at 5 years and 55.7% versus 50% at 9 years (log-rank test P = .5). CONCLUSION Our study has shown that HOHD and HHD patients had similar hospitalization rates, but patients on HOHD had better rehabilitation and shorter hospitalizations for all-cause morbidity. Despite this, HHD and HOHD patients had similar survival rates.

BACKGROUND AND AIMS The previous study showed a higher prevalence of coronavirus (COVID-19) in end-stage renal disease (ESRD) patients than in the general population (3.1% versus 0.1%). The presence of COVID-19 infection significantly increased the mortality rate of patients on dialysis compared to non-COVID patients (20.2% versus 0.2%). To date, no clear guidelines exist for the management of COVID-19 in renal patients. Bamlanivimab is a potent neutralizing monoclonal antibody that blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into human cells, which could potentially lead to therapeutic benefit. To our knowledge, this is the first study to use bamlanivimab in COVID-19+ haemodialysis (HD) patients with the aim to determine the effect of bamlanivimab on the mortality of these patients. METHOD We conducted a retrospective case-control study across a single HD centre of non-hospitalized HD patients, with documented positive SARS-CoV-2 testing. We analysed the period from October 1 to November 14 2021, in which COVID-19+ patients were dialyzed in our institution. Cases were defined as HD patients who received bamlanivimab and controls were patients who did not receive bamlanivimab. Descriptive statistics, including chi-squared and Mann–Whitney U test, were performed. We used multinomial logistic regression to find the independent relationship between bamlanivimab use, disease severity, coronary artery disease (CAD), heart failure and 1-month mortality risk. RESULTS Patients who received bamlanivimab frequently had the chronic obstructive pulmonary disease (COPD) than those in the control group. There were no significant differences between groups in any of the other parameters assessed (Table 1). Besides higher baseline ferritin levels in the control group, no other significant differences in biochemical markers were found between examined groups (Table 2). Over a 1-month follow-up, one patient (7.7%) died in the bamlinivimab group, while 8 patients (44.4%) died in the control group. Multinomial logistic regression revealed that no bamlanivimab treatment was given. CAD and disease severity increased the risks of mortality 39.1 times (P = 0.12), 81.7 times (P = 0.08) and 99.9 times (P = 0.04), respectively. CONCLUSION In COVID-19+ HD patients, bamlanivimab has been a safe and effective treatment method, lowering mortality although not statistically significant. We also discovered that having a more severe clinical presentation at baseline, as well as having a CAD, was related to a greater risk of mortality. Our findings imply that larger, more conclusive clinical studies of bamlanivimab in HD patients with COVID 19 should be conducted.

Background: Traditional models of intracranial dynamics fail to capture several important features of the cerebral windkessel. Experiments show that the cerebral windkessel is a band-stop filter tuned to the heart rate, which is not consistent with existing pressure-volume compartment models. Flow MRI studies in humans reveal expansion and relaxation of the cranial contents during the cardiac cycle that continuously opposes arterial expansion and relaxation, and we suggest this is the way the windkessel is implemented in the cranium. This systolic-diastolic brain motion is analogous to the loading and unloading of the capacitor plates in the model circuit.Methods: In this study, we use exogenous input autoregressive (ARX) modeling of a simple band-stop electrical circuit to model the cerebral windkessel of normal dogs. We compare the circuit waveforms to waveforms measured in dogs, and we examine the dynamics that underlie the cerebral windkessel.Results: Our ARX analysis shows close agreement between the circuit and the windkessel, which implies similar physical mechanisms of pulsation suppression. This correspondence between physiological data and circuit dynamics suggests that the cerebral windkessel is a frequency-sensitive band-stop filter for the passage of arterial power through the cranium. Another perspective from which to understand the windkessel is to consider the smooth offset and the pulsatile components of cerebral arterial flow as DC and AC power respectively. In the cranium, DC power of cerebral blood flow passes through the capillary bed to the veins and AC power is diverted through the CSF to the veins. This windkessel mechanism optimizes smooth capillary flow and minimizes potentially damaging capillary pulsatility.Conclusions: Our windkessel model provides substantial new insights into intracranial dynamics, cerebral blood flow and capillary circulation, and it provides a new framework for the study and treatment of several common disorders of intracranial dynamics such as cerebral edema, hydrocephalus, pseudotumor cerebri, and Cushing’s reflex.

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 Acute kidney injury (AKI) secondary to urinary obstruction is a common urological-nephrological problem. In this retrospective study, our goals were to describe the etiology, management and outcomes of patients with obstructive nephropathy who were hospitalized at Nephrology Department during 2019. Method AKI was defined by the RIFLE classification. Diagnosis of obstruction was defined by ultrasound imaging, intravenous pyelography and CT scan. Results During 2019 AKI secondary to urinary obstruction was diagnosed to 64 patients. 73% of them were male, average age 65 ± 16 years. About 60% of the patients had bilateral hydronephrosis, chronic kidney disease and anuria duration longer than 24h. The following desobstructive procedures were applied: urinary catheterization to 33 patients, percutaneous nephrostomy tube to 14 patients, double-J stent to 7 and other procedures to 10 patients. The most common causes of obstruction were malignancy and benign prostatic hyperplasia 60%, calculosis 17%, and other causes 20% such as neurogenic bladder and retroperitoneal fibrosis. As many as 30% of patients required acute hemodialysis treatment, of which 6% remained on a chronic program in period of three months. Out of all, 30% of patients had a partial recovery of kidney function, while 20% had complete recovery. The most common complication was infection and bleeding. The univariate logistic regression, adjusted for age and hemodialysis treatment, has shown that significant independent predictors for chronic kidney disease progression were anuria duration >24h (RR 2.21; 95% CI 0.014-1.03; p=0.05), polyuria duration (RR 2.11; 95% CI 1.112-3.98; p=0.02) and duration of hospital treatment (RR 9.16; 95% CI 2.102-39.94; p=0.03). The most significant predictor of death was duration of hospital treatment (RR 9.16; 95% CI 2.102-3.399; p=0.003). Multivariate logistic regression did not shown significance any of the above risk factors. Conclusion Given that third of patients with obstructive nephropathy require acute HD, 6% remain in chronic HD, and almost one third require rehospitalization, close cooperation between a nephrologist and urologist is required. Rapid desobstructive procedures and careful monitoring after desobstruction is warranted. Requirement of regular screening remains opened for obstruction in vulnerable populations.

Background and Aims It is well-known that interstitial changes in patients with focal-segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are linked with disease chronicity and progression. The aim of this study was to analyze is there any connection between interstitial changes and outcome after “first line” therapy in patients with FSGS/MCD. Method From 2014 till 2019, biopsy proven diagnosis of FSGS/MCD was established in 40 patients. Interstitial changes were classified in three groups as following: 0-w/o changes; 1-mild changes; 2-severe changes. Patients with nephrotic syndrome (No=29) were treated with prednisolone (1mg/kg) and after six months we have registered therapy outcome as: CR-complete remission; PR-partial remission; EX-death; NO-no effect. Results Among treated patients (age 50.4±15.3 years, 15 men), CR was achieved in 10 patients (34.5%) and 6 out of these 10 (60%) had no interstitial changes. Partial remission was observed in 11 patients (37.9%), in 4 patients (13.8%) therapy did not have any effect, and 4 patients (13.8%) deceased (table 1). All patients in EX and NO group had interstitial changes. There were no significant difference in age, gender, proteinuria, albuminaemia, creatinine and glycaemia levels between groups except for hemoglobin levels that were significantly lower in EX group than in others (∑ 15.144; p=0.002) and urea levels that were significantly higher in EX group (∑ 138.057; p=0.024). Conclusion Patients with FSGS/MCD respond well on standard immunosuppressive protocol, particularly in absence of interstitial changes what may increase the chance for achieving complete remission.

Background and Aims Heparin-induced thrombocytopenia (HIT) is a potentially fatal adverse reaction after administration of unfractionated or fractionated heparin, which underlies the generation of antibodies to the heparin complex and platelet factor 4 (PF4). It occurs in 5% of patients treated with unfractionated heparin and 0.5 - 1.5% fractionated heparin. The aim of the study is to determine the incidence and outcome of hemodialysis patients with HIT over 4-years period. Method This retrospective study analyzed patients who were tested for evidence of positive anti-heparin antibody in the period from 2015 to 2020 in Zvezdara University Medical Center. The diagnosis was confirmed by the 4T clinical scoring system, a positive antiheparin-PF4 ELISA test and a positive platelet aggregation test with heparin. Results During observation period, total of 64 tests were performed, out of which 23 patients were positive. Out of them, 14 patients were on HD, 7 patients (geriatric, surgery and cardiology departments) received therapy due to peripheral thrombosis, AIM or arrhythmia and 2 patients during 2020 due to SARS-CoV-2 bilateral pneumonia. All patients treated at nephrology, started hemodialysis (HD) with unfractionated heparin, while others were treated with LMWH. 4T scoring showed that 64% of patients had a moderate risk of developing HIT, while high risk was assessed in 36% of patients. Thrombotic complications in the form of deep venous thrombosis had 53% of patients and pulmonary thromboembolism had 17,5 % of patients. The greatest decrease in Tr was the most commonly observed between 10th and 14th day (61% of patients) and 39% from 4th to 10th day from start of heparin administration. In addition to heparin withdrawal and treatment with alternative non-heparin anticoagulation (fondaparinoux), 7 patients needed plasma treatment. 11 patients on HD were transferred to peritoneal dialysis (PD), and 3 patients recovered renal function. Overall mortality was 52%, and it was below 30% in hemodialysis patients. Conclusion HIT should be considered in patients at risk. It is necessary to abolish heparin treatment and use alternative method (PD) or alternative anticoagulation. Hemodialysis patients have better prognosis than other comparable patients

Membranoproliferative glomerulonephritis (MPGN) is characterized by mesangial cell proliferation and structural changes in glomerular capillary walls and double-contoured glomerular basement membrane (GBM). Usually, it is connected with cryoglobulinemia which is defined by the presence of a circulating, a cold-precipitating immunoglobulin. The chemical and immunological features of the cryoglobulins are used to define three types of cryoglobulinemia. In this report we describe the third case of MPGN type II with essential cryoglobulinemia without HCV infection, which is usually defined in the literature as MPGN type II. Here, we present 61-years old woman previously diagnosed with MPGN in 2012 at another institution. At that time, she was not examined in terms of cryoglobulinemia. Initially she was treated with pulses of methylprednisolone, then oral corticosteroids until cessation when complete remission was achieved. Meanwhile, she had two relapses of the disease. In October 2020 we re-evaluated her and found out positive cryoglobulins in repeating testing. Serological studies for anti-neutrophil cytoplasmic antibodies (ANCA), myeloperoxidase and proteinase 3, anti-double stranded DNA antibodies, anti-hepatitis C antibodies, anti-HIV antibodies and anti-hepatitis B surface antibodies were all negative. Serum M protein or monoclonal IgM were not detected. Percutaneous renal biopsy was compatible with the diagnosis of MPGN. Based on clinical, laboratory and histological evaluation, it was concluded that the patient had a MPGN with essential cryoglobulinemia. Therapy with mycophenolate mofetil had a beneficial effect on the course of disease and the patient achieved partial remission and stabile renal function for the last 3 months of follow-up. Since the therapy for MPGN with essential cryoglobulinemia is not standardized, further research in the field is needed.

Background and Aims Outcome of dialysis patients differ considerably across the globe and many studies confirmed that home-based treatments offer some advantages, not only in regard of quality of life but also regarding of patients’ outcome. History of home hemodialysis (HOHD) in our country dates from 1971. and since that time many patients were treated with this dialysis modality. HOHD changed over the time together with general improving of dialysis techniques and we aimed to analyze the results of treatment of our population treated by HOHD during different time points. Method We analyzed patients characteristics, dialysis and uremia-related complications and survival of patients on HOHD during three different time points: 2001. (No=70), 2011. (No=29) and 2019. (No=22). Results The most frequent reason for ESRD in 2001, 2011 and 2019. was glomerulonephritis (48%, 45%, 36% respectively), followed by polycystic kidney disease 24% in 2011. and 36% in 2019. Diabetes mellitus (DM) was rarely cause of ESRD: in 2001. 2.1%; 4.5% in 2019. and none in 2011. In 2001. the patients were more frequently treated using high flux membranes (HF) as compared to HDF (87.1% vs.12.9%), and through years this changed in favor of HDF (48% vs. 52% in 2011, and 13.6% vs. 86.4% in 2019). Anti HCV prevalence was 27.4%, 38%, 27%, in 2001, 2011. and 2019. respectively. Anemia status was better controlled in recent years revealed by Hb level: 10.5±2.0 g/dl in 2001, 12.1±1.6 in 2011. and 11.9±2.3 in 2019. with almost similar percentage of patients treated with ESA (31%, 28% and 36% respectively). In 2001, parathyroid hormone level (iPTH) was 379±236 pmol/l and only 20% of patients underwent parathyroidectomy while in 2011. and in 2019. parathyroidectomy was performed in 69% and 59% of patients respectively. Therefore, in 2011. and in 2019. mean iPTH level was 33.8±48.5 and 40±46.2pmol/l respectively. Kaplan-Mayer analysis confirmed ten-year survival of 42% for period 1982-2001, and the most frequent reasons for death were infection and cardiovascular diseases. During the period 2011. to 2019., ten-year survival was 88% and cardiovascular diseases led to death in most of the cases. Conclusion our results have shown that HOHD treatment improved through the years considering patients’ survival, anemia status and secondary hyperparathyroidism treatment. Apart from HDF, the other factors have to be taken into consideration.

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.

Background and Aims Heparin-induced thrombocytopenia (HIT) is a potentially fatal adverse reaction after administration of unfractionated or fractionated heparin, which underlies the generation of antibodies to the heparin complex and platelet factor 4 (PF4). It occurs in 5% of patients treated with unfractionated heparin and 0.5 - 1.5% fractionated heparin. The aim of the study is to determine the incidence and outcome of hemodialysis patients with HIT over 4 years period. Method Our retrospective study analyzed patients who were tested for evidence of positive anti-heparin antibody in the period from 2015 to 2019 in Zvezdara University Medical Center. The diagnosis was confirmed by the 4T clinical scoring system, a positive antiheparin-PF4 ELISA test and a positive platelet aggregation test with heparin. Results During observation period, total of 54 tests were performed on HIT suspected patients, out of which 21 patients were positive. Out of them, 14 patients were on HD, and other 7 (geriatric, surgery and cardiology departments) received therapy due to peripheral thrombosis, AIM or arrhythmia. All patients treated at nephrology, started hemodialysis (HD) with unfractionated heparin, while others were treated with LMWH. 4T scoring showed that 64% of patients had a moderate risk of developing HIT, while high risk was assessed in 36% of patients. Thrombotic complications in the form of deep venous thrombosis had 50% of patients, pulmonary thromboembolism had 11% of patients. The greatest decrease in Tr was most commonly observed between 10th and 14th day (61% of patients) and 39% from 4th to 10th day from start of heparin administration. In addition to heparin withdrawal and treatment with alternative nonheparin anticoagulation (fondaparinoux), 5 patients needed plasma treatment. 11 patients on HD were transferred to peritoneal dialysis (PD), and 2 patients recovered renal function. Overall mortality was 52%, while in nephrology patients was below 30%. Conclusion HIT should be considered in patients at risk. It is necessary to abolish heparin treatment and use alternative method (PD) or alternative anticoagulation. Hemodialysis patients have better prognosis than other comparable patients.

Background and Aims Increased free radicals production and down-regulated antioxidant enzymes activities contribute to protein, lipid and DNA oxidative damage particularly in HD patients lacking for GSTM1 enzyme activity. At the same time, those patients exhibit higher mortality rate than those with active GSTM1 genotype. It has been shown that vitamin E-coated membranes (VitEM) may decrease oxidative stress and inflammatory status in overall HD patients. Therefore, for the first time we analyzed VitEM dialyzers in patients who are homozygote for GSTM1 gene deletion and in whom anti-oxidative and anti-inflammatory benefit could be the greatest. Method GSTM1 genotypes were determined by PCR in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VitEM, while other forty were dialyzed with high-flux polysufone membranes of the same surface. Markers of protein and lipid oxidative damage, inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined at the start and at the end of the study. Results Seventy-five patients’ finished the study. There were no significant differences in baseline characteristics between the two groups (age, sex, body weight, dialysis vintage, vascular access, presence of diabetes, dialyzers surface, Kt/V and CRP). Also, there were no significant differences at baseline markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, thiol groups increased significantly in both groups, but without statistical significance between groups (Table 1). SOD did not change significantly during three month period. IL-6 increased in control group, at the same time decreased in VitEM group, but without statistical significance. Conclusion Vitamin E-coated membranes did not influence markers of oxidative stress in HD patients with GSTM1-null genotype. Further studies in the field are required.

Background and Aims According to previous data, the prevalence of tunnelled cuffed vascular catheters (TCC) is more frequent in elderly as compared to younger HD patients. Still, it is not clear if elderly have decreased survival of TCC as compared with survival in younger. Method During the period from January 2010 to June 30, 2015, 110 permanent catheters were implanted in 64 patients (1.72 catheters per patient, 51.6% male mean age 67±12years, 20 diabetics). Out of all patients, 44 (68.7%) were older than 65 years, 12 (27.3%) were diabetic and 11 (25%) were previously treated with peritoneal dialysis. In the age-based subpopulations we compared the incidence of infections, thrombosis, chemical removal of thrombus by actilysis and TCC outcome. Results Reasons for TCC placement in elderly were inability of the second option and exhausted vascular approach and these reasons were found to be significantly more frequent compared to patients younger than 65 years (p = 0.020 ). Primary position of TCC was right jugular vein in both groups (39.1%, No = 25 vs 14.1% No = 9), more commonly in group of elderly patients, but there was no significant difference in the initial TCC position depending on the age structure of the patient (Hi square = 1.720, p = 0.886). The overall incidence of infections was 3.44 episodes per 1000 catheter days and patients' age did not affect TCC replacement, infection, thrombosis and inflammation. In the group of elderly, 27 patients had catheter infection (61.4%), 10 (22.7%) had catheter thrombosis and actilysis resolved thrombosis in 6 (13.6%) patients without significant difference as compared with younger patients. Catheter-induced bacteraemia were more common in TCC over 65 years (47 TCC vs. 12 TCC) but without statistical significance (p = 0.062). Similarly, exit site infection, was more common (14 TCC vs. 4 TCC) for those older than 65 years but also without statistical significance. Thrombosis of TCC occurred in 7 patients with TCC younger than 65 years and in 20 TCC in cohort of elderly (Hi square = 0.033, p = 0.535) (Table 1). Regarding treatment outcome, 19 (43.2%) elderly patients died while being treated with TCC, 12 patients (27.3%) changed treatment modality to peritoneal dialysis, 4 patients (9.1%) received arteriovenosus graft (AVG) and 9 patients had functional TCC at the end of follow up (20.5%) and no significant difference was found in the outcome compared to younger patients. Conclusion The reason for placement of TCC in elderly is the inability of other treatment options and exhaustion of vascular access. Concerning catheter related complication and outcome, there was no significant difference between the elderly and younger patient.

Background and Aims Serum levels of parathyreoid hormone is the main cause of mineral disorders in patients on chronic hemodialysis, and it well known that this hormone acts as an uremic toxine and contributes to oxidative stress and overall mortality rate. However, there are many observations which imply that the protean manifestations of renal bone disease cannot be explained simply by abnormalities of PTH or vitamin D metabolites. For example, levels of PTH correlate relatively poorly with various parameters of bone histology. It has been shown that uremia leads to cytokijne imbalance with overbalance of proinflammatory citokines such as TNF. Also, studies showed that calcimimetic therapy decreases not only PTH levels, but also levels of TNF. The aim was to analyse tumor necrosis factor (TNF) gene polymorphisms in group of hemodialysis patients and to correlate the findings with presence of secondary hyperparathyroidism. Method This cross sectional study included 202 patients on regular hemodialysis for more than six months in University Medical Centar Zvezdara. Venous blood for genotyping and for PTH analysis was collected on midweek dialysis session from each patient. Genetic analysis was performed by using polymerase chain reaction. Patients are diveded in two groups regarding the level of PTH, so that first group had normal PTH levels or mild SHPT, while patients in second group had sever SHPT. We analysed influence of genetic polymorphism for TNF on apperance of SHPT. Results The results have shown 3 fold lower risk for developing SHPT in GG homozygots for TNF gene with statistical significance (p=0,01)- Table 1. Conclusion Parathyreoid gland hyperfunction is multifactorial disorder and there are emerging evidence that cytokines as endogenous modulators have an important impact on its pathogenesis.

Background: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. Methods: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. Results: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. Conclusions: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.

BackgroundSodium thiosulphate (NaTS) is mostly used in haemodialysis (HD) patients with calcific uraemic arteriolopathy. This double-blind, randomized, placebo-controlled study assessed the effect of NaTS on progression of cardiovascular calcifications in HD patients.MethodsFrom 65 screened patients, we recruited 60 patients with an abdominal aorta Agatston calcification score ≥100. Thirty patients were randomized to receive NaTS 25 g/1.73 m2 and 30 patients to receive 100 mL of 0.9% sodium chloride intravenously during the last 15 min of HD over a period of 6 months. The primary endpoint was the absolute change of the abdominal aortic calcification score.ResultsThe abdominal aortic calcification score and calcification volume of the abdominal aorta increased similarly in both treatment groups during the trial. As compared with the saline group, patients receiving NaTS exhibited a reduction of their iliac artery calcification score (−137 ± 641 versus 245 ± 755; P = 0.049), reduced pulse wave velocity (9.6 ± 2.7 versus 11.4 ± 3.6; P = 0.000) and a lower carotid intima-media thickness (0.77 ± 0.1 versus 0.83 ± 00.17; P = 0.033) and had better preservation of echocardiographic parameters of left ventricular hypertrophy. No patient of the NaTS group developed new cardiac valve calcifications during the trial as compared with 8 of 29 patients in the saline group. By univariate analysis, NaTS therapy was the only predictor of not developing new valvular calcifications. No adverse events possibly related to NaTS infusion were noted.ConclusionsWhile NaTS failed to retard abdominal aortic calcification progress, it positively affected calcification progress in iliac arteries and heart valves as well as several other cardiovascular functional parameters.

Cardiovascular calcifications (CVC) are present in up to 70% of non-diabetic dialysis patients. Sparse data are available on predictors of very long-term outcomes of such patients. The Belgrade Aachen Study on Calcification in Hemodialysis patients (BASCH study) aimed to study this using a comprehensive CVC assessment. We prospectively analyzed 220 hemodialysis patients followed for a mean of 76 months (median 73 months, range 6–160 months). We compared patients deceased from cardiovascular diseases (CVD) and survivors. Analyses included composite calcification scores (determined by combining ultrasound and X-ray analyses), demographic, clinical and laboratory data and pulse wave velocity (PWV). For survival analysis, patients were divided into group according to quartiles (Q). Compared to survivors, deceased patients from CVD were significantly older, more frequently hypertensive, had shorter dialysis times per week and lower Kt/V values, and they exhibited lower serum fetuin A, osteoprotegerin and hemoglobin as well as higher CRP levels. Composite calcification and Adragao scores were significantly higher in deceased patients from CVD as was PWV. Mean survival was 101 ± 47 months (Q1), 87 ± 51 month (Q2), 66 ± 48 (Q3) and 54 ± 45 months (Q4), p = 0.000. Cox multivariate regression analysis showed that independent predictors for cardiovascular mortality were composite calcification score in the range of third and fourth quartiles. Composite calcification score emerged as significant predictors of long-term survival in our group of largely non-diabetic dialysis patient population, finding that should be confirmed by intervention studies.

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.

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 Microscopic polyangiitis (MPA) is one of the causes of the pulmonary–renal syndrome associated with elevated non-specific markers of inflammation and antineutrophil cytoplasmic autoantibody (ANCA) positivity in 50–75%. De novo occurrence of the disease in patients on chronic hemodialysis (HD) has not been described. Case presentation We presented patient who developed MPO-ANCA-associated MPA with lung and musculoskeletal involvement after 4 years on regular HD due to bilateral nephrectomy. After excluding the other causes of MPO-ANCA positivity, diagnosis was confirmed even without renal biopsy. Patient received standard immunosuppression therapy and he is still in remission after 27 months. Conclusion The onset of immune-mediated disease could be observed even after introduction of renal replacement therapy, which may be a diagnostic problem. Early recognition and traditional immunosuppressive regiment may provide successful outcome.

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.