Abstract Introduction: Frailty is a state of increased vulnerability to physical stressors. It is common in patients with end-stage renal disease (ESRD) who are on hemodialysis (HD). The aim of this study was to analyze the presence of frailty phenotype among HD patients and to evaluate their interrelationship with different biochemical markers. Methods: For the frailty assessment the Frailty Phenotype by Fried et al. was used, where frailty was reported if three of the following criteria were met: unintentional weight loss, self-reported exhaustion, weakness, slow walking speed and low physical activity. From 281 HD patients, 126 patients were frail, 58 were pre-frail (two criteria were met) and the rest of the study population were robust (97 patients). BMI was calculated for all patients and venous blood samples were taken to determine laboratory parameters for bone alkaline phosphatase (BAP), phosphate (P), potassium (K), C-reactive protein (CRP) and albumin. Results: Patients who were on HD longer than 60 months have more characters of frailty. (p=0.019). A statistically significant positive correlations between frailty score and BAP (rho = 0.189; p = 0.001), and CRP (rho = 0.233; p < 0.001) were observed, and significant negative correlations between frailty score and albumin (rho = - 0.218; p < 0.001) and K (rho = - 0.198; p = 0.001). Conclusions: The associations of frailty with markers of mineral bone disorder, inflammation and nutrition indicate the importance of these parameters in the indirect assessment of the frailty phenotype in HD patients.

Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications. A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs. At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p<0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p<0.05), P04 (p<0.001), CRP (p<0.011), SBP and DBP (p<0.05). HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.

Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at a high risk of acquiring SARS-CoV-2 and of developing severe COVID-19 and death. The possibility of being reinfected with this virus is poorly understood. To date, there are a small number of reports of reinfections in COVID-19 patients, especially in HD patients, with only four cases described so far. The aim was to show the possibility of reinfection and developing severe acute respiratory syndrome in HD patients. We describe a 69-year-old ESRD patient who had been on HD treatment for three years, with diabetes mellitus and a history of ischemic cardiomyopathy. The patient was tested for SARS-CoV-2 by a nasopharyngeal polymerase chain reaction (PCR) test because of a positive cluster at his dialysis unit and initially diagnosed with COVID-19 in July 2020. In this period, he had mild symptoms for a few days and remained asymptomatic afterwards. Four months later, he presented to the hospital with fatigue, high fever and shortness of breath, and was COVID-19 positive again. This case points to the possibility of reinfection, lack of immune response after an asymptomatic or mild infection, or even the possibility of the fi rst false-positive PCR test. Future longitudinal studies are needed to evaluate the potential reinfections, recurrence, and duration of antibody detection.

The occurance of mid- and longterm uremic complications is related to the low clearance rate of middle and large molecule uremic toxins when hemodialysis (HD) alone is adopted. As the uremic toxins and their corresponding biological effects become increasingly clear, blood purification treatment that aims to remove these toxins, has developed from a stage of life-sustaining to improving the quality of life. The objective of this study was to evaluated demographic, clinical and laboratory data in patients who underwent the combination of maintenance hemodialysis with hemoperfusion (HP) and in those who recieved HD alone and to investigate whether this combination could improve the clearance rate of middle and large molecule uremic toxins. A total of 26 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into three groups: Group 1 (7 patients) received combined treatment of HD with HP biweekly (HD 2 times a week with HD+HP once a week), whereas Group 2 (10 patients) was given HD with high flux dialyzer and Group 3 (9 patients) was given HD with low flux dialyzer 3 times a week. This study was followed for 4 months. Before and after the observational period demographic and clinical data were taken from the medical history and blood samples were taken for hemoglobin (Hb), iron (Fe), total iron binding capacity (TIBC), albumin (Alb), calcium (Ca), phosphorus (P04) and parathyroid hormone (PTH). This study included 13 female and 13 male patients with a mean age of 41, 62 + 11.12 and a mean dialysis duration of 62, 78+53, 33 months. When it comes to baseline characteristics, patients of the group 3 were significantly older than patients in other groups (p=0.001). At the end of the four months observation period, the same difference according to age was noticed (p=0.01). Also, HD+HP group had significantly higher values of TIBC (p=0.006) and significantly lower serum levels of P04 (p=0.001). EPO doses were very similar in group 1 and 2, but in group 3 there were noticeably lower than in those two groups but without a significant difference. The serum levels of albumin were higher in group 3 compared to the other two groups but also without statistical difference. No statistical difference between groups after the follow up period was observed in terms of Hb, Fe, PTH, Ca, BMI, duration of dialysis treatment and vascular access. When groups are viewed individually, in the HD+HP group serum P04 levels were significantly lower after the 4 months off the follow up period than it was at the beginning (p=0.031) and also TIBC was significantly higher (p=0.018). In group 2 the values of TIBC were significantly lower after the follow up period than it was at the beginning (p=0.025). No significant difference was noticed in group 3 but serum PTH levels tends to decrease after 4 months compared to baseline measurement. This combination treatment of HD with HP was superior to HD in reducing levels of phosphorus. These findings suggests a potential role of reducing the risk of cardiovascular events in this population especially when it is known that hyperphosphatemia has been pointed out as the primary culprit in the process of cardiovascular calcification. Also, patients who underwent the combined treatment showed higher values of TIBC but unfortunately no difference was noticed between Hb levels and EPO doses. These results eventually demonstrates their role in the improvement of renal disease anemia, which opens up the possibility of further research on a larger sample and over a longer period of time.

Introduction: Plasmapheresis is often used as a therapy in the treatment of thrombotic thrombocytopenic purpura (TTP). TTP is manifested in thrombotic microangiopathy, consumed thrombocytopenia, hemolytic anemia and acute kidney injury with HUS development, neurologic dysfunction, and fever. Case report: we will present a case of a patient with acute kidney injury and refractory TTP at the beginning of hospitalization, subsequently manifested in secondary nephrotic syndrome. The patient was a female, 39 years of age, who as an emergency case was referred from the hospital in East Sarajevo to the Clinic of Endocrinology, Diabetes and Metabolism Disorders of the Clinical Center University of Sarajevo with suspected TTP. A few days before hospitalization she had a fever and vomiting, and therefore consulted her physician. She was hospitalized due to severe general condition, generalized edema, visible body hematomas, and diuresis amounting to 600 ml/12 hours. Laboratory results on admission were as follows: Leukocytes 19.5, Erythrocytes 3.23, Hemoglobin 103, Hematocrit 28.8%, Platelets 65.4 with few schistocytes and 2 reticulocytes, Sodium 140 mmol/L,, Potassium 4.5 mmol/L, Calcium 1.90 mmol/L, Glucose 7.9 mmol/L, Urea 37.5 mmol/L, Creatinine 366 umol/L,, Bilirubin 19.0 umol/L, Lactate dehydrogenase 1194 U /L. The patient was communicative, in cardiopulmonary sufficient state. Central venous catheter was placed in the right jugular vein and the first plasmapheresis was performed. During the hospitalization 38 plasmapheresis treatments with frozen plasma were performed, followed by three Rituximab treatment cycles. After the last plasmapheresis treatment a platelet count was 138. Also, parameters of the renal function were in their referent values. At the beginning of the treatment proteinuria was 19.6 g/24 hours urine. We were faced with a dilemma whether renal biopsy should be repeated in the future given that it might be the case of primary and not secondary nephrotic syndrome. Controlled proteinuria was 4.7g after plasmapheresis. The patient used only Prednisolone at a dose of 10 mg daily and although initially diagnosed with acute kidney injury she was not treated with dialysis. Conclusion: early diagnosis and early start of plasmapheresis therapy is vital for treatment of patients with acute kidney injury and TTP (HUS). A small number of patients is refractory to plasmapheresis and introducing Rituximab and plasmapheresis treatment is recommended.

Abstract Introduction. Bone disease is a chronic complication of chronic kidney disease and major clinical problem in hemodialysis (HD) patients. The aim of our study was to assess the influence of treatment longevity on biochemical parameters of mineral and bone metabolism in HD patients, and to identify the most important parameters. Methods. The research was observational and retrospective, involved 70 patients, mean age 58.69±12.54, divided into groups in respect to the duration of dialysis treatment (Group I-5 years, Group II-5-10 years and Group III-over 10 years). Results. Serum phosphorus was increased, but the values tend to increase along with dialysis duration - (Group I: 1.93±0.45; Group II: 1.97±0.50; Group III: 2.01±0.37; p>0,05). Calcium values were also not significantly increased based on the duration of treatment [Group I: 2.3 (2.2-2.41); Group II: 2.46 (2.15-2.6), Group III: 2.35 (2.10-2.52)]. Dialysis and PTH correlated positively in the first group of patients (Rho=0.470, p=0.013). The values of calcium and alkaline phosphatase correlated positively in all patients (Rho=0.351, p=0.003). PTH was significantly higher in the second and third compared to the first group (p=0.009 and p=0.038, respectively), and there was no significant difference between the second and the third group. Interestingly, parathyroidectomized patients had higher PTH values compared to those without parathyroidectomy (557 vs. 359 pg/ml). Conclusion. The most reliable marker for clinical monitoring of bone disease in dialysis patients is PTH. The values of calcium and phosphorus are highly variable and not reliable parameters for bone disease follow-up.

Introduction Leptin is a cytokine-like hormone which has a complex role in inflammation. However, the importance of leptin in the pathogenesis of rheumatoid arthritis (RA) is far from being fully elucidated. The aim of the study was to determine serum leptin levels in RA patients and to evaluate whether there is an association between disease activity, anthropometric indices and leptin levels. Material and methods This hypothesis-generating study included 55 RA patients and 25 matched healthy subjects. The serum leptin concentration was determined by enzyme-linked immunosorbent assay (ELISA). Results Median serum leptin level in RA patients of 27.4 ng/ml (14.5–54.9 ng/ml) was statistically significantly higher (p = 0.03) compared with the median leptin value of 16.3 ng/ml (9.6–38.8 ng/ml) determined in healthy controls. The serum leptin level in the high disease activity group was significantly higher (p < 0.0005) than that in the low disease activity group and in healthy controls. A significant difference (p = 0.001) in serum leptin level was also found when the high disease activity group was compared with the moderate disease activity group. In the RA group a statistically significant positive correlation (rho = 0.390; p = 0.003) was observed between serum leptin level and disease activity score (DAS28). Conclusions The present results show that serum leptin levels are increased and significantly associated with disease activity in patients with RA and may have a valuable role in the inflammatory reactions and pathogenesis of RA.

Objectives: We hypothesized that serum heart fatty acid binding protein (HFABP) levels could be affected by hypertension in addition to renal impairment in patients on hemodialysis. The aim was to find out possible association between serum HFABP and hypertension in patients treated by hemodialysis. Methods: The cross-sectional study included 72 patients, both gender, age 18-78 years who were recruited from Clinic for Hemodialysis, University Clinical Center Sarajevo. According to Kidney Disease Outcomes Quality Initiative criteria for hypertension, patients were distributed into 2 groups: normotensive (HD-N) and hypertensive (HD-H) group. The cardiac biomarker HFABP was measured using ELISA kit Human FABP3 (Elabscience Biotechnology Co.,Ltd), on immunoanalyzer STAT FAX 2100, USA. The kidney functional biomarkers were measured spectrophotometrically using automated analyzer. Results: Serum HFABP level was lower in HD-H group (3.02(1.96-4.13) ng/mL) compared to serum HFABP in HD-N group (3.38(1.98-5.37) ng/mL)(p=0.359). Patients in HD-N group were older and treated by hemodialysis for a longer time than those in HD-H group (p<0.001 and p=0.029, respectively). Conclusion: Serum HFABP level in normotensive patients on hemodialysis is not significantly different compared to hypertensive patients suggesting that heart type fatty acid binding protein might not be significantly affected by hypertension in hemodialysis patients. Keywords: HFABP, hemodialysis, blood pressure, cardiovascular risk

Introduction: Renalase is a protein secreted in kidneys and considered as a blood pressure modulator. High rates of hypertension and its regulation in patients on hemodialysis demands search for potential cause and treatment. The aim of this study was to determine the genotype and allele frequencies of renalase gene rs2576178 polymorphism in population from Bosnia and Herzegovina. Also, the objective of present study was to find the possible association between renalase gene rs2576178 polymorphism and hypertension in patients on hemodialysis. Material and Methods: The genotype of renalase gene rs2576178 polymorphism was determined in 137 participants (100 patients on hemodialysis and 37 controls), using polymerase chain reaction (PCR) and subsequent cleavage with MspI restriction endonuclease. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium using a Chi-squared test. The value of P<0.05 was considered as statistically significant. Results: Comparison of genotype distribution and allele frequency in participants on hemodialysis with and without hypertension, and healthy control showed no statistical difference. Conclusion: The results of the study suggest that renalase gene rs2576178 polymorphism is not a factor that influences blood pressure in patients on hemodialysis.

Abstract Introduction. Cardiovascular diseases are the leading cause of death in hemodialysis patients. The decline of residual renal function increases the prevalence and severity of risk factors of cardiovascular morbidity and mortality in these patients. Hypertension is common in dialysis patients and represents an important independent factor of survival in these patients. Methods. The study included 77 patients who are on chronic HD for longer than 3 months. Depending on the measured residual diuresis patients were divided into two groups. The study group consisted of patients with residual diuresis >250 ml/day, while patients from control group had residual diuresis <250 ml/day. All patients had their blood pressure measured before 10 consecutive hemodialysis treatments. Collected data were statistically analyzed using SPSS 16.0. Results. The study included 77 hemodialysis patients, mean age of 56.56±14.6 years and mean duration of hemodialysis treatment of 24.0 months. Of the total number of patients, 39(50.6%) had preserved residual renal function. Hypertension was more common in the group of patients who did not have preserved residual renal function (68.4% vs 25.6%). There was statistically significant negative linear correlation between the volume of residual urine output and the residual clearance of urea and values of systolic blood pressure [(rho=−0.388; p<0.0001); (rho=−0.392; p<0.0005)], values of mean arterial pressure [(rho =−0.272; p<0.05); (rho=−0.261; p=0.023; p<0.05)] and values of pulse pressure in hemodialysis patients [(rho =−0.387; p<0.001); (rho=−0.400; p<0.0005)]. Conclusions. Residual renal function plays an important role in controlling blood pressure in patients on hemodialysis. More attention should be directed to preserve residual renal function, and after the start of hemodialysis by avoiding intensive ultrafiltration with optimal antihypertensive therapy.

Objective: Despite advances in the technology of dialysis, cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD) who are on hemodialysis therapy are still very high. Recent clinical studies have demonstrated a significant correlation between leptin levels and hypertension, hyperlipidemia, perturbed fibrinolysis and chronic inflammation. The aim of this study was to investigate the significance of changes in serum leptin concentrations and relationship of leptin and traditional cardiovascular risk factors in patients with varying duration of hemodialysis therapy. Design and method: The cross sectional study included 60 patients with end stage renal disease, of both sexes, divided into two equal groups (n = 30) based on the duration of hemodialysis treatment: A group of subjects who are on hemodialysis therapy between three months and five years, and group of subjects who are on hemodialysis therapy five and more than five years. The control group (n = 30) consisted of apparently healthy subjects, with no subjective and objective indicators of chronic renal disease. The serum leptin concentration was determined by enzyme-linked immunosorbent assay (ELISA). Results: Serum leptin levels in patients in Group under 5 years was significantly higher from leptin concentrations in serum of patients in Group eqally and more then 5 years and of serum leptin concentrations in the control group. Statistically significant positive correlation was found between serum leptin levels and body mass index (BMI) in subjects of Group eqally and more then 5 years and in the control group. There was no significant correlation between serum leptin levels and C – reactive protein (CRP) in any of the groups of patients. Results showed that the serum leptin value had a poor diagnostic accuracy in distinguish hemodialysis patients from healthy control, as well as, hemodialysis patients at different length of dialysis therapy. Conclusions: In this population of stable HD patients, obtained results do not support the hypothesis that serum leptin and relationship between leptin and traditional cardiovascular risk factors can be used as an independent marker to distinguish between hemodialysis patients than healthy subjects, nor in differentiating hemodialysis patients at different length of dialysis therapy.