The frailty phenotype in hemodialysis patients and its association with biochemical markers of mineral bone disorder, inflammation and nutrition.

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.

Leptin is associated with disease activity but not with anthropometric indices in rheumatoid arthritis patients.

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.

Treatment of Acute Kidney Injury in Hemolythic Uremic Syndrome (TTP).

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.

Renalase Gene rs2576178 Polymorphism in Hemodialysis Patients: Study in Bosnia and Herzegovina.

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.

Mortality in hemodialysis patients over 65 years of age.

INTRODUCTION: Based on the statistics the population in Bosnia and Herzegovina is getting older. In 2013 the average life span for women was 73.6 years and 68.1 for men. The chronic hemodialysis program is mainly reserved for elderly patients with high mortality risk. The most common cause of hemodialysis mortality relates to cardiovascular diseases (60.2%), regardless of frequent innovations and improvement of hemodialysis procedures. THE AIM OF THE STUDY: was to determine the mortality rate by age groups with comments on the presence of non-traditional predictors (anemia, hypoalbuminemia, CRP, vascular access and PTH) in dialysis patients in the follow-up period of 36 months. METHODS: The study included all patients undergoing chronic hemodialysis treatment at the Clinic of Hemodialysis of the Clinical Center University of Sarajevo (CCUS). RESULTS: Out of a total number of hemodialysis patients (n=232), the specific mortality rate in patients under 65 years of age was 16.8%, and 50.5% in patients over 65 years of age. According to the age groups the mortality rate in elderly patients is as follows: from 65 to 74 years (45.1%), from 75 to 84 years (55.0%), over ≥85 years (75.0%). The most frequent vascular access in patients under and above 65 is arteriovenous fistula (79.6% and 62.1 %), temporary hemodialysis catheter (11.7% and 43.8 %) and long-term hemodialysis catheter (8.8% and 4.2 %). In the age group under 65 years of age the temporary hemodialysis catheter is significantly and more frequently used in diseased patients in respect to survivors (34.8% vs. 7.0%) [χ(2)(2)=15.769, p=0.001]. Diseased patients from the age group over 65 had a significantly lower mean value of haemoglobin in blood (M=100.9±17.5 g/L) in respect to survivors (M=109.2±17.1)[t(93)=2.339; p=0.021], lower mean value of albumin in blood (Me=32.0; IQR=29.0 do 35.0) in respect to survivors (Me=34.0; IQR=32.0 to 38.0) [U=762.5; p=0.006], and higher mean value of CRP in blood (Me=19.3 mg/L; IQR=6.6 to 52.0) in respect to survivors (Me=7.8; IQR=4.0 to 16.7) [U=773.5; p=0.008]. Diseased patients belonging to the age group over 65 had lower mean value of PTH, but without statistical significance (p>0.05). CONCLUSION: older age, temporary vascular access, anaemia and hypoalbuminemia are strong predictors of mortality in hemodialysis patients. Old age does not present contraindication for hemodialysis treatment, and treatment of terminal renal illness should not be abandoned.

Correlation Between C-reactive Protein and Non-enzymatic Antioxidants (Albumin, Ferritin, Uric Acid and Bilirubin) in Hemodialysis Patients.

INTRODUCTION: Increased levels of C-Reactive Protein are found in 30-60% on hemodialysis patients and it is closely associated with the progression of atherosclerosis, cardiovascular morbidity and mortality. Non enzymatic antioxidants are antioxidants which primarily retain potentially dangerous ions of iron and copper in their inactive form and thereby prevent its participation in the production of free radicals. AIM: The aim of the study was to examine the relationship of CRP and non enzymatic antioxidants (albumin, ferritin, uric acid and bilirubin) i.e. examine the importance of CRP as a serum biomarker in assessing the condition of inflammation and its relationship to antioxidant protection in patients on hemodialysis. METHODS: The study was cross-sectional, clinical, comparative and descriptive. The study involved 100 patients (non diabetic) on chronic hemodialysis. The control group consisted of 50 subjects without subjective and objective indicators of chronic renal disease. In all patients, the concentration of CRP as well as concentrations of non enzymatic antioxidants were determined. RESULTS: In the group of hemodialysis patients 60% were men and 40% women. The average age of hemodialysis patients was 54.13 ± 11.8 years and the average age of the control group 41.72 ± 9.8 years. The average duration of hemodialysis treatment was 91.42 ± 76.2 months. In the group of hemodialysis patients statistically significant, negative linear correlation was determined between the concentration of CRP in and albumin concentration (rho = -0.251, p = 0.012) as well as negative, statistics insignificant, linear correlation between serum CRP and the concentration of uric acid (r = -0.077, p = 0.448). Furthermore, the positive, linear correlation was determined between serum CRP and ferritin (r = 0.159, p = 0.114) and positive linear correlation between CRP and total serum bilirubin (r = 0.121, p = 0.230). In the control group was determined a statistically significant, positive, linear correlation between serum CRP and uric acid concentration (rho = 0.438, p = 0.001) and statistically significant, positive, linear correlation between serum CRP and total serum bilirubin (rho = 0.510, p = 0.0001) A statistically significant, negative linear correlation was determined between CRP and albumin concentration (rho= -0.393, p = 0.005) as well as statistically significant, negative linear correlation between serum CRP and ferritin control group (rho = -0.391, p = 0.005). CONCLUSION: Elevated CRP level is a strong and independent predictor of low levels of serum albumin, which indicates that the hypoalbuminemia in hemodialysis patients could be more due to inflammation than malnutrition. There was no statistically significant correlation between CRP and other non enzymatic antioxidants (uric acid, ferritin, bilirubin), which shows that indicators of antioxidant defense in hemodialysis patients must be individually measured to determine their actual stocks and activity.

[The effect of intradialytic exercise program on the quality of life and physical performance in hemodialysis patients]. / Ucinak intradijaliznog programa vjezbanja na kvalitetu zivota i fizicke mogucnosti u hemodijaliziranih pacijenata.

AIM: To determine the effect of a 16-week intradialytic exercise program consisting of 30 minutes of exercise during the first two hours of dialysis with three times a week frequency, on the quality of life (QoL), level of depression/anxiety and physical perfor- mance in hemodialysis (HD) patients. METHODS: The clinical, longitudinal, prospective study with one-group repeated measures design was conducted during a 16-week period. A convenience sample of 52 HD patients, who had been on HD for a minimum of 6 months, were included. QoL, level of depression and anxiety (questionnaires: SF-36, Back Depression Inventory (BDI) and Back Anxiety Inventory (BAI)) and physical performance (modifying Visual Analogue Scale (VAS) and Manual Muscle Testing (MMT)) were assessed at baseline and after 4-month exercise program. RESULTS: The following scales of SF-36 questionnaire were improved after 16-week exercise program: role functioning/emotional (P=0.01 8), energy/fatigue (P = 0.002) and social functi- oning (P = 0.030). Level of depression and anxiety were significantly decreased in males (P = 0.007 and P = 0.022, respectively) and females (P = 0.001 and P = 0.000, respectively). VAS scale and MMT were significantly increased in males (P = 0.000 and P = 0.001, respectively) and females (P = 0.01 9 and P = 0.001, respectively) after 16-week exercise program. CONCLUSION: Exercise program improves some aspects of QoL and physical performance, and decreases the level of depression and anxiety in HD patients.

[Tunneled catheter infections in patients on hemodialysis--one center experience]. / Infekcije tuneliranih katetera kod pacijenata na hemodijalizi--iskustvo jednog centra.

INTRODUCTION: Central venous catheters in hemodialysis patients can be used as vascular access for hemodialysis. At our clinic, our doctors use temporary and tunneled catheters for hemodialysis treatment. The presence of the catheter, increases the risk of bacteremia in hemodialysis patients. Risk factors are nasal colonization with Staphylococcus aureus, prolonged use of catheters, previous bacteremia, anover dose of iron, low hemoglobin, low albumins, diabetes mellitus, and surgical procedures. The aim of this study was prevention of catheter sepsis and timely disclosures of existing and effective cures. PATIENTS AND METHODS: Thirty-eight patients with tunnelled catheters as vascular access for hemodialysis were included into the study. The study was conducted between January 1, 2011 and January 3, 2012. Outof 38 patients, 60% (23) were male and 40% (15) were female, while the average age was 67.48 +/- 13.9 years. The duration of hemodialysis treatment was 108.9 +/- 16.54 months. RESULTS: Over the study period, 9 patients developed bacteriemia associated with the use of catheter as a vascular approach. The incidence of infection in our study was 3.5 cases per 1000 catheter days. Two patients (5.2%) developed an infection in the first three months after the day of catheter placement, and the remaining 6 (15.8%) patients after one year of the use of catheter as a vascular approach. Regarding the causes of infection, in 3 (33%) patients these were gram-positive pathogens, in 5 (56%) patients gram-negative pathogens, and in one (11%) patient it was polimicrobe flora. According to the protocol and pending the outcome of susceptibility testing (antibiogram), all the patients were prescribed with antibiotic treatment therapy. In 7 (75%) patients tunnelled catheter was removed and replaced with temporary catheters for hemodialysis treatment. In 2 (25%) patients, was antibiotic-lock solution was injected into the catheter. There were no significant differences (p<0.05) in age, duration of dialysis treatment, hemoglobin levels, iron, transferrin saturation, ferritin and albumin in patients without infection and those who developed an infection. Only one patient has had a nasal colonization with Staphylococcus aureus. One patient developed severe thrombocytopenia, followed by sepsis anda lethal outcome due to heavy gastrointestinal bleeding. CONCLUSION: tunneled venous catheter is the increasingly common vascular access with the hemodialytic patients, but it is also a common cause of infection. Proper care and use of catheters, making the unique protocols of care and treatment algorithm occupy a significant place in each hemodialysis center. Our goal is to prevent the catheter sepsis, and to promptly detect the existing and a fast treatment of the same.

Effects of treatment with L-thyroxin on glucose regulation in patients with subclinical hypothyroidism.

AIMS: We examined effects of treatment with 1-thyroxin on glucose regulation in patients with subclinical hypothyroidism. METHODS: The study included 100 patients, ages 51.75 +/- 13.23 years, BMI = 27.97 +/- 4.52 kg/m2, with SH (TSH > 4.2 mU/L and with normal level of T3 and T4). Laboratory evaluation included serum free T3, free T4, TSH, thyroid antibodies, TGL, insulin, C-peptide and glucose during OGTT, HbA1c, CRP and level of lipids. Percentile, average and correlation analysis have been utilized in statistical analysis. Twelve patients with SH had GI and 38 patients had DM. All patients were treated with low dose of 1-thyroxin (25-50 ug) and high physical activity. RESULTS: After 6 months treatment with 1-thyroxin, patients had normal or limited TSH (5.85 +/- 0.92 vs. 3.54 +/- 0.55 mU/L), level of fasting insulin (114.64 +/- 24.11 vs. 96.44 +/- 17.26 pmol/l) significantly decreased, HbA1c (6.74 +/- 1.01 vs. 6.26 +/- 1.12) decreased as well. The level of CRP significantly decreased as well (2.27 +/- 0.8 vs. 3.32 +/- 1.1 mg/l). The changes were and in level of total cholesterol (5.39 +/- 0.57 vs. 6.10 +/- 0.67 mmol/l), triglyceride levels (1.69 +/- 0.37 vs. 2.22 +/- 0.49 mmol/l), HDL cholesterol (1.16 +/- 0.14 vs. 1.03 +/- 0.15 mmol/l) and LDL cholesterol (3.79 +/- 0.64 vs. 4.37 +/- 0.77 mmol/l). The correlation between TSH and HbA1c was positive and significant (r = 0.46). CONCLUSION: The normalization of TSH resulted in decrease of level of fasting insulin, fasting and postprandial glucose, CRP and lipids. Higher CRP associated with fasting hyperinsulinemia before insulin resistance has been evidenced in most patients with SH. These data support an important role of treatment of SH in support of glucose regulation.

[Prevention and treatment of hepatitis C infected patients on hemodialysis]. / Prevencija i lijecenje hepatitisa C kod pacijenata na hemodijalizi.

INTRODUCTION: Hepatitis C virus infection (HCV) is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: In this prospective, observational study, 205 patients, 37 (18%) of them with chronic HCV infection, were followed up for a one-year period at Department of Hemodialysis, Sarajevo Clinical Center, University of Sarajevo. The following parameters were analyzed: dialysis duration, sex, PCR RNA, HCV genotypes and biochemical parameters. Thirteen anti-HCV PCR RNA positive patients were treated with pegylated interferon alpha (Pegasys, Hoffman-La Roche). The goal of therapy was to reach sustained virologic response. The presence of anti-HCV antibodies in serum was detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Of 37 anti-HCV positive patients, there were 20 (54%) males and 17 (45.9%) females with the mean hemodialysis duration of 143.67 +/- 57.64 months and mean age of 54.45 +/- 8.93 years. Of 37 anti-HCV positive patients, 30 (81.08%) patients were HCV RNA PCR positive. Among HCV RNA PCR positive patients, two had up to twofold elevated ALT values, one had twofold elevated AST values, and one had sixfold elevated GGT values. Thirteen RNA PCR positive patients were treated with pegylated interferon alfa for 48 weeks. Only one patient had genotype 1 virus. Upon therapy completion, only three patients were negative by PCR RNA (genotype 1b, 23.07%) at six months and yearly follow ups remained PCR negative. CONCLUSION: Sustained virologic response was achieved in three study patients. Monitoring guidelines for infection control, isolation of seropositive patients, and strict hygienic preventive measures can prevent HCV seroconversion in hemodialysis patients.

The Importance of HbA1c Control in Patients with Subclinical Hypothyroidism.

GOAL: To investigate the correlation between TSH and HbA1c in the treatment of L-thyroxine in the process of glycemic control in patients with subclinical hypothyroidism. PATIENTS AND METHODS: The sample consisted of 100 patients, mean age 51.75±3.23 years, BMI=27.97±4.52 kg/m(2), with SH (TSH>4.2 mU/L and normal serum T3 and T4). Laboratory diagnosis included the determination of free T3, free T4, thyroid antibodies, Tg, insulin, C-peptide and glucose during the OGTT, HbA1c, CRP and lipid levels. 20 patients with SH had prediabetes and 38 patients had DM. All patients were treated with low doses of L-thyroxine (25-50ug) and all were physically active. RESULTS: After 6 months of treatment with L-thyroxine, the patients had normal or decreased TSH (5.85±0.92 vs. 3.54±0.55 mU/L), insulin levels (114.64±24.11 vs. 96.44±17.26 pmol/L) significantly reduced HbA1c (6.74±1.01 vs. 6.26±1.12) is reduced. CONCLUSION: The correlation between TSH and HbA1c was positive and significant (r=0.46). This indicates a significant effect of treatment with L-thyroxine on glycemic control in patients with subclinical hypothyroidism.

Evaluation and treatment of cardiovascular diseases in patients on hemodialysis--single center experience.

AIM: To evaluate frequency of CVD in dialysis population, in relationship to patients with and without diabetes, and their most common treatment. PATIENTS AND METHODS: This retrospective study included 187 patients, 106 males and 81 females, divided in two groups, diabetics and non-diabetics, treated by chronic hemodialysis. Patients' analyses included: anamnesis, ECG, chest X-rays, echocardiogram, laboratory examinations for calcium (Ca), phosphorus (P), parathormone (PTH), cholesterol (chol), triglicerids (TG), C-reactive protein (CRP), hemoglobin (Hb) and uric acid. In addition, we analyzed groups of drugs used by patients as prescribed by cardiologists. RESULTS: Average age was 58.0 years, most of them between 51 and 60. Average hemodialysis length was 4 years. Primary kidney diseases were pyelonephritis and glomerulonephritis. 19,78% of patients had diabetes. 165 patients (88,23%) had one or more cardiovascular diseases. 110 patients (58,2%) had hypertension, most of them used ACE inhibitors. Using test of multiple correlation, statistically significant correlations, among others, were shown between BMI and Ca, uric acid and P, albumin and PTH in diabetics, at the statistical significance level at p < 0.05. CONCLUSION: Cardiovascular diseases are the most common comorbidity and cause of mortality in hemodialysis population. There was no statistical significance in age, however there is a statistical difference in the dialysis duration variable, but in some biochemical laboratory parameters there was some difference. ACE inhibitors were most commonly used in the treatment of hypertension and systolic dysfunction, alone or with beta-blockers.