This issue of the International Journal of Nephrology focused on kidney diseases within a devil's triangle, oxidative stress (OS), mediators, inflammation, specifically relating to the clinical significance of identification, and prevention. Every creature in need of oxygen faces OS. It has a critical role in the molecular mechanisms of renal injury in several kidney diseases, and many complications of these diseases are mediated by OS, mediators, and inflammation. There is a complex relationship between these three; mostly they induce each other. While some of the diseases themselves can contribute to OS, reactive oxygen species (ROS) produced by activated leukocytes and endothelial cells in sites of inflammation cause tissue damage. Although inflammation looks dangerous for the organism, it is a normal reaction of organs and tissues to protect themselves against several invasion(s). It enables the immune system to remove the injurious stimuli and initiate the healing process of tissues. However, the interactions between OS, mediators, and inflammation may result in glomerular damage, proteinuria, electrolyte, and volume instabilities which cause nephron loss, on the long view. Detailed studies on this topic are included in this issue. The kidney can easily be damaged by ROS, due to the rich structure of long-chain polyunsaturated fatty acids. The article by E. Ozbek summarizes the induction of OS within kidney in several conditions, including diabetes, hypertension, hypercholesterolemia, obesity, aging, urinary obstruction, environmental toxins, and molecular mechanisms of these inductions in the light of existing literature data. Diabetic nephropathy is one of the most common microvascular complications of type 1 and type 2 diabetes mellitus and the leading cause of end-stage renal disease worldwide [1]. Rojas-Rivera et al. reviewed the biological bases of oxidative stress and its role especially on diabetic nephropathy, as well as the role of the Keap1-Nrf2 pathway, and recent clinical trials targeting this pathway with bardoxolone methyl, a novel synthetic triterpenoid with antioxidant and anti-inflammatory properties. Obesity continues to be a public health problem throughout the world. Epidemiologic studies have shown that 66% of adults and 16% of children and adolescents are overweight or obese [2]. Obesity-related glomerulopathy is an increasing cause of end-stage renal diseases. J. Tang et al. stressed the chronic low-grade systemic inflammation in obesity and discussed the roles of inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible treatment modalities to prevent kidney injury in obesity, such as the usage of anti-IL-6 receptor antibody, TNF-α antagonist, adiponectin, nutritional and surgical interventions to reduce OS. Hypertension is an another important global health issue both in adults and children. It is one of the major risk factors for the progression of kidney diseases. The relationship between blood pressure and dietary sodium and salt sensitivity has been well known, and renal sodium handling is a key determinant of long-term blood pressure regulation [3]. There is a limited knowledge in the literature regarding the role of ROS-mediated fibrosis and renal proximal tubule sodium reabsorption through the Na/K-ATPase. S. Liu et al. reviewed the possible role of ROS in the regulation of Na/K-ATPase activity. The authors emphasized the importance of further researches whether ROS signaling is a link between the Na/K-ATPase/c-Src cascade and NHE3 regulation and how OS, stimulated by high salt and cardiotonic steroids, regulates Na/K-ATPase/c-Src signaling in renal sodium handling and fibrosis. Urotensin-II is the most potent mammalian vasoconstrictor identified to date, almost tenfold more potent than endothelin-I [4]. A. Balat and M. Buyukcelik discussed the role of urotensin-II on renal hemodynamics and its possible role on several kidney diseases, such as the minimal change nephrotic syndrome. The article includes a detailed discussion of urotensin-II immunoreactivity in renal biopsy specimens of children with membranoproliferative glomerulonephritis, membranous nephropathy, IgA nephropathy, Henoch-Schonlein nephritis, and focal segmental glomerulosclerosis. Because of its complex relation with OS and other mediators, authors describe it as “more than a mediator” in glomerular diseases. They briefly mention from the effectiveness of U-II antagonism, as a new promising pharmacological treatment target in some kidney diseases. Given the potential impact of OS, mediators, and inflammation trio, the importance of prevention has come into question. Strong evidence indicates the importance of new molecules that are able to diminish them which in turn may help to decrease the prevalence and/or progression of several kidney diseases. Therefore, further researches are needed to the better understanding of the molecular and clinical mechanisms of this triad. They may help to provide new therapeutical strategies to control several complications in patients with kidney diseases. Ayse Balat Halima Resic Guido Bellinghieri Ali Anarat

Pacijenti s kroničnom bubrežnom bolešću (HBB) imaju smanjeni odgovor na vakcinaciju zbog općeg slabljenja imunološkog sustava povezanog s uremijom. U odnosu na vakcinaciju u pacijenata bez HBB-a, na primjer, dijalizni pacijenti imaju niži titar antitijela i nemogućnost održavanja adekvatnog titra antitijela tijeNovi protokol vakciNacije pacijeNata Na hemodijalizi protiv hepatitisa B iskustvo jedNog ceNtra

Methylenetetrahydrofolate Reductase (MTHFR) is key enzyme in metabolism of homocysteine. Homozygotes for mutation (TT genotype) have hyperhomocysteinemia, risk factor for atherosclerosis development. The aim of the study was to find out distribution of genotype frequencies of C677T MTHFR among patients on maintenance hemodialysis. Possible association of alleles and genotypes of C677T polymorphism of the MTHFR gene with age of onset, duration of dialysis and cause of kidney failure was studied also. Cross-sectional study includes 80 patients from Clinic of Hemodialysis KUCS in Sarajevo. In order to perform genotyping, isolated DNA was analyzed by RFLP-PCR and gel-electrophoresis. From total of 80 patients, 42.5% (n=24) were female, 57.5% (n=46) were male, mean age 54.59+/-1.78 years and duration of dialysis 79.92+/-6.32 months. Genotype distribution was: CC 51.2% (n=41), CT 37.5% (n=30) and TT 11.2% (n=9). Patients with wild-type genotype have longer duration of dialysis in month (87.1 +/- 63.93) comparing to TT genotype patients (67.06 +/- 39.3), with no statistical significance. T allele frequency was significantly higher in group of vascular and congenital cause of kidney failure (Pearson X2 =6.049, P<0.05) comparing to inflammation etiology group. Genotype distribution results are within the results other studies in Europe. Obtained results indicate that C677T polymorphism is not associated with onset, duration and cause of kidney failure in our hemodialysis population. There is an association of T allele of the MTHFR gene and vascular and congenital cause kidney failure.

Each haemodialysis treatment requires the application of anticoagulation medicines, which will prevent coagulation in extracorporal blood circulation. In this study we try to determine the quality of admitted anticoagulant and his effect on lipid profile on hemodialysis patients after twelve months. We were applying standard heparin and low weight molecular heparin (LWMH). During our study we was analyzed effect of anticoagulant therapy on lipid profile of hemodialysis patients. In that parameters was included triglycerides, cholesterol, lipoprotein fractions, complete blood count, Hgb, HCT; All of these parameters was analyzed in correlation with duration of hemodialysis treatment, sex and age of the patients. Our research was carried out as a prospective study, for the period of 12 months. In the study were included 60 patients (34M/26F), who were on chronic hemodialysis program. All patients were divided into two groups. The first group of patients was included 27 patients (15M/12F) who were treated with standard heparin. The second group was included 33 patients (19M/14F) treated with LWMH (enoxaparin). The average length of hemodialysis was 4.15 +/- 0.52 years. Each patient had a protocol in which is marked parameters such as flushing dialysator, creating fibrin-ring in vein and arterial dropper and the time it takes to stop the bleeding. In the results the average age amounted to 58.54 +/- 2.24 years. The average value of cholesterol in the blood was 5.38 +/- 2.26. Values of HDL-cholesterol in patients treated with LWMH were significantly lower (P<or=0.05) in the treated group compared to standard heparin. There were no significant statistical differences between both groups in relation to the level of LDL cholesterol in the blood. (p ns). LWMH had a better effect on the irrigation system and dialysator on both sex equally, compared with standard heparin. LWMH is in the female dialysis population has led to improvements in lipid profile. After the first six months of study in male patients treated with standard heparin in relation to the female part of the observed patients was significantly better anticoagulation effect in the first half of the study (1.85 +/- 0.05 compared to 2.09 +/- 0.10) (P<or=0.001). Average rating blood clots were statistically significant for standard heparin (p<or=0,001) with 1,86 at the beginning the value is fell to 1.41, while for LWMH with 1.85 at the beginning of the study amounted to 1.52 grade average. (P<or=0.05). The results of our study show that LWMH had a better rinsing effect of dialysis systems and dialysator in both sex equally, compared to standard unfractioned heparin. When the male part of the respondents in the first six months of standard heparin had a better evaluation of blood clots than women in the same group, and also better than the group on enoxaparin for both gender. LWMH in female dialysis population has led to improved lipid profiles. Patients treated with standard heparin had a statistically significant reduction in the rate of blood clots than patients who received enoxaparin (LWMH). Such differences were minimal, which can be interpreted by the fact that LWMH still derivative of the standard heparin.

INTRODUCTION Cardiovascular diseases are the most frequent causes of morbidity and mortality in patients with chronic renal disease. The aim of our paper is to evaluate the risk factors of cardiovascular complications in patients with various stages of chronic renal disease (CRD), with or without diabetes mellitus (DM). PATIENTS AND METHODS The study included 98 patients with different stages of the CRD, with creatinine clearance <60 ml/min/1.73m2, and laboratory parameters monitored: homocysteine, BNP, cholesterol, LDL, HDL, HbA1c, Body Mass Index (BMI). First group comprised 49 patients with DM, age 50-82 years, M 28/F 21. Second group comprised 49 patients without DM, age 35-80 years, M 18/F 31. The IMT (intima media thickness) was measured by B-mode ultrasonography, and all patients had echocardiography examination done by 2D Doppler ultrasonography. RESULTS The IMT values in diabetic patients had statistically significant positive correlation with homocysteine values of r=0.9393, p<0.034, and cholesterol r=0.289, p<0.05, compared to non-diabetics. A significant negative correlation was found between the ejection fraction (EF) and BMI in both groups, more prominent in non-diabetics r=0.289, p<0.044 (diabetics r=0.162, p>0.05). 47.4% of diabetics had arteriosclerotic changes on carotid arteries, 8.5% had stenosis of ACC, and 22.0% had rhythm abnormalities on ECG. A positive correlation between IMT and BMI was found in diabetics, but was not statistically significant r=0.111, p>0.05. In the diabetics group a significantly higher (p<0.05) values of BNP, HbA1c, proteinuria, BMI, and cholesterol were found, and significantly lowered EF (p<0.0001). CONCLUSION Risk factors for cardiovascular complications in patients with DM are various, and the most pronounced significance was found in the values of homocysteine, BNP and cholesterol.

Renal Registry (RR) of Bosnia and Herzegovina was established in 2002, with aim to follow up the trends of Renal Replacement Therapy in Bosnia and Herzegovina. The prevalence of Renal Replacement Therapy (RRT) in Bosnia and Herzegovina is rising steadily. One reason for this is an increasing number of patients starting RRT. The aim is to present the epidemiology and treatment of all aspects of RRT in Bosnia and Herzegovina in period 2002-2008. Centre-related and patient-related questionnaires were sent to all 25 dialysis centres in Bosnia and Herzegovina. The demographic data, prevalence and incidence, type of renal replacement therapy, cause of ESRD, erythropoietin administration, cause of death, and type of vascular access were obtained from the questionnaires. Collected data were analysed using SPSS statistics. The number of patients treated by Renal Replacement Therapy (RRT) increased steadily from 1,531 patients in 2002 to the 2,206 at the 2008 (43%). The prevalence has increased from 399 pmp in 2002 to 696 pmp. in 2008. Incidence (new patients) in 2002 was 110 pmp and incidence rate in 2008 was 163, and there were 249 new patients (day 1). The mean age for new patients increased from 60 years in 2002 to 63.5 years in 2008 and the population over 75 years rate from 8.79% to 11.3%. Most ESRD patients in Bosnia and Herzegovina are undergoing intermittent hemodialysis (92%), while some patients (8%) are treated by peritoneal dialysis and transplantation. The most significant cause of ESRD in 2008 was chronic glomerulonephritis (421 patients, 19.2%), followed by pyelonephritis (414 patients, 18.9%), BEN (14.7%) and Diabetes mellitus (12.2%). Hepatitis B and C virus infections had 397 (16.3%) patients, out of them 22 had both type of infections and 98 patients had B type infection. Only 10.5% of patients were tested on MRSA and 3 patients were positive on MRSA. There were no HIV-positive patients on RRT. The most common type of vascular access was AV fistula in 85% patients, AV graft 2% and catheters in 13%. Out of hemodialysis patients, 85.7% received ESA almost s.c. The median weekly dose was 4,000 UI. Cardiovascular diseases were the leading cause of death, gross mortality rate of dialysis patients being 13.01% in 2008. The need for RRT in Bosnia and Herzegovina is increasing and the number of patients increased by 43% since 2002. Hemodialysis is still the most common modality of treatment (92%), while proportion of PD and transplantation is slowly increasing. The preventive measures are necessary to prevent ESRD and also to decrease the number of patients on dialysis.