The GSTO2 (rs156697) Polymorphism Modifies Diabetic Nephropathy Risk.

Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes' distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p < 0.001, p < 0.001, p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances.

Gender-specific differences in hemodialysis patients: a multicenter longitudinal study from Serbia.

PURPOSE: The study was undertaken with the aim to determine gender-specific differences in incident hemodialysis (HD) patient and their changes over time. METHODS: The retrospective longitudinal closed cohort study involved 441 incident patients starting HD in 2014 and followed for 1-59 (median 43, IQR 40) months. Demographic, clinical data, treatment characteristics, laboratory findings and outcome were abstracted from the patients' medical records. RESULTS: The relative number of males on HD was about twice that of females throughout the five years investigated. At the beginning of the study, no significant differences were found in the main demographic and clinical characteristics except that diabetes was more often the underlying disease in men than in women. Systolic blood pressure decreased over time significantly more in females than in males. Throughout the study spKt/V was significantly higher in females than in males, but it increased in patients of both genders. There were no gender differences for comorbidities, vascular access and the majority of laboratory findings except for higher serum levels of creatinine and CRP in men than in women. Relatively more females were treated with erythropoiesis stimulating agents and phosphate binders than males. Age and malignancy were selected as significant predictors of mortality for both genders, and, in addition, polycystic kidney disease, serum level of albumin and CRP for men, but spKt/V for women. CONCLUSION: Some significant gender differences were observed throughout, while others appeared during the study but none of them were due to gender inequalities in the applied treatment.

Plasma activity of the antioxidant enzymes in predicting diabetic nephropathy progression.

INTRODUCTION: The aim of the study was to examine whether biomarkers of oxidative stress are predictors of diabetic nephropathy (DN) progression. METHODS: The study involved 45 patients with type 2 diabetes and DN and 15 healthy controls. Patients were followed for 3 years and the annual percentage change in eGFR was used to estimate the progression of DN. Patients with an annual percentage change in eGFR above the cutoff value of - 5.48%/year were classified in group 1, those with an annual percentage change in eGFR ≤ - 5.48%/year in group 2. RESULTS: The 28 patients in group 1 had the annual percentage change in eGFR of - 4.78 and 39.12%/year, and for the 17 patients in group 2 it ranged from - 24.86 to - 6.18%/year. At the onset of the study no significant differences were found between the groups in demographic, clinical or laboratory parameters. Plasma activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly lower in patients than in the controls. During 3-year study kidney function and size changed insignificantly in group 1, while eGFR and kidney size decreased and proteinuria increased significantly in group 2. Multivariate linear regression analysis selected male gender, duration of diabetes, systolic blood pressure, fasting serum glucose, urine protein/creatinine ratio as factors associated with DN progression. Plasma activity of GPX and SOD were selected as positive predictors of annual percentage change in eGFR. CONCLUSION: Besides already known factors, plasma activity of GPX and SOD were found to be significant independent predictors of DN progression.

Association of SOD2 (rs4880) and GPX1 (rs1050450) Gene Polymorphisms with Risk of Balkan Endemic Nephropathy and its Related Tumors.

Background: Experimental data show that superoxide dismutase 2 (SOD2) is involved in ochratoxin (OTA)-induced nephrotoxicity, whereas clinical data indicate the role of SOD2 rs4880 or glutathione peroxidase 1 (GPX1) rs1050450 polymorphisms in end-stage renal disease and urothelial carcinoma risk, known to be the major complications of Balkan endemic nephropathy (BEN). Therefore, we hypothesized that SOD2 and GPX1 gene polymorphisms would influence the risk of BEN and its associated tumors. Materials and Methods: The study was conducted in 207 BEN patients and 86 controls from endemic areas. Results: Individuals with both copies of variant SOD2 allele, known for lower mitochondrial antioxidant protection, are at a significantly higher BEN risk (OR = 2.6, p = 0.021). No association was observed between GPX1 gene polymorphism and BEN risk. Combining SOD2 and GPX1 genotypes did not alter the risk of BEN development. Regarding the risk of urothelial tumors in BEN patients, none of the polymorphisms studied was significantly associated with the risk of these tumors. Conclusions: Polymorphism in SOD2 rs4880 gene affects the risk of BEN development. Hence, SOD2 genotyping could, together with a panel of other enzymes, be used as a biomarker of susceptibility in BEN areas.

Increased Glomerular Filtration Rate in Early Stage of Balkan Endemic Nephropathy.

Background: A previous study indicated that Balkan endemic nephropathy (BEN) patients in the early stage of the disease had significantly higher creatinine clearance (Ccr) than healthy persons. The aim of the study was to assess whether tubular creatinine secretion affects Ccr in early stages of BEN and to check the applicability of serum creatinine-based glomerular filtration rate (GFR) equations in these patients. Methods: The study involved 21 BEN patients with estimated GFR (eGFR) above 60 mL/min/1.73 m2, excluding any conditions that could affect GFR or tubular creatinine secretion, and 15 healthy controls. In all participants Ccr with and without cimetidine and iohexol clearance (mGFR) were measured and eGFR calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease Study (MDRD) equations. Glomerular hyperfiltration cutoff (GFR-HF) was calculated. Results: There was no significant difference between the groups in Ccr before and after cimetidine or for eGFR, but mGFR was significantly higher in BEN patients than in controls (122.02 ± 28.03 mL/min/1.73 m2 vs. 101.15 ± 27.32 mL/min/1.73 m2; p = 0.032). Cimetidine administration reduced Ccr by 10% in both groups. The ratio of Ccr to mGFR was significantly above one in seven BEN patients and five controls and their mGFR values were similar. Seven other patients and eight controls had this ratio equal to one, while values below one were recorded for seven more patients and two controls. mGFR of all these 14 patients was significantly higher than that of healthy controls (129.88 ± 27.52 mL/min/1.73 m2 vs. 107.43 ± 19.51 mL/min/1.73 m2; p = 0.009). Mean GFR-HF was significantly higher than mGFR in controls, but these two values were similar in BEN patients. eGFR underestimated mGFR in both BEN patients and controls. Conclusion: The ratio of Ccr to mGFR and mGFR to GFR-HF indicated that elevated mGFR in early stages of BEN could be explained by increased glomerular filtration, but tubular creatinine secretion augmented Ccr in a smaller proportion of patients, who did not differ from healthy subjects.

Differences in Risk Factors and Prevalence of Vascular Calcification between Pre-Dialysis and Hemodialysis Balkan Nephropathy Patients.

Aims: The aim of this study was to compare the risk factors and prevalence of vascular calcification (VC) in pre-dialysis and hemodialysis (HD) patients with Balkan endemic nephropathy (BEN) or other kidney diseases (non-BEN). Materials and Methods: The study involved 115 patients, 32 pre-dialysis and 83 HD patients, separated into groups of BEN and non-BEN patients. In addition to interviews, objective examinations and laboratory analyses, VC was assessed using Adragao score. Results: Patients with BEN were significantly older in both groups, while pre-dialysis BEN patients had significantly lower systolic blood pressure, serum cholesterol and phosphorus levels, but higher urinary excretion of phosphorus than non-BEN patients. These differences were lost in HD groups. In pre-dialysis patients, prevalence of VC was lower in BEN than in non-BEN group and mean VC score differed significantly between them (2.8 (1.7) vs. 4.6 (1.8); p = 0.009). No significant difference in VC score was found between BEN and non-BEN patients on HD. Multivariate analysis showed that in pre-dialysis patients VC score >4 was associated with lower iPTH and higher serum cholesterol level, but in the HD group with higher serum triglyceride level and longer HD vintage. Conclusions: Lower prevalence of risk factors for VC in the BEN than non-BEN patients was found in pre-dialysis but not in HD group and this was reflected in the prevalence and severity of VC in the groups. Prevalence of VC and mean VC score were significantly lower in pre-dialysis BEN than in non-BEN patients but not for those on HD.

Recording blood pressure and eGFR in primary care after the Belgrade screening study.

BACKGROUND: In 2009, Belgrade nephrologists and general practitioners from thirteen health centers carried out screening for chronic kidney disease (CKD). Three years later, medical records of patients from four health centers participating in the screening study were retrospectively analyzed in order to check whether general practitioners had continued to control patients at risk for CKD in accordance with the recommendations provided. METHODS: The study included 460 patients who visited their doctor at least once in the three-year period. Data on blood pressure, ACEI use, estimated glomerular filtration rate (eGFR) and comorbidities were taken from patients' medical records. RESULTS: Blood pressure was not recorded in any of the three years in 42.8% and eGFR in 36.7% of the patients, but blood pressure was registered every year in 7.8% and eGFR in 4.3% of them. Over the three years, the relative number of patients with recorded blood pressure decreased from 41.7% to 17.8%, and with recorded eGFR from 41.7% to 21.5%. Multivariate linear regression found that Health Center, systolic and diastolic blood pressure and presence of hypertension were negatively associated with number of years with recorded blood pressure. Health Center, systolic blood pressure and sum of years with recorded eGFR below 60 ml/min/1.73m2 were associated with number of years with recorded eGFR. CONCLUSIONS: Under-recording of blood pressure and eGFR in primary care health centers suggests lack of adherence to current guidelines and insufficient care of CKD patients. This implies the necessity for continuous education of physicians.

Comparison of accepted and unaccepted living kidney donors: one-center experience.

BACKGROUND: Kidney transplantation from living donors (LD) has stagnated in many countries. This study aimed to check whether correction of LD selection practice could increase the number of kidney transplantations. METHODS: From January 2003 to December 2012, 241 potential adult LD were evaluated in our hospital. Outcome (mortality and end-stage renal disease-ESRD) of accepted LD (182) was compared with unaccepted (59) donors. RESULTS: Mortality of LD was comparable with that for the standardized Serbian population (SMR = 1.104; 95% CI (0.730-1.606). Among evaluated potential LD, almost every fourth had been unaccepted, but reasons were modifiable in 42.4% of them. In pre-donation period unaccepted donors were significantly older, measured glomerular filtration rate was lower, with higher 15-year and lifelong projected ESRD risks than accepted donors. Despite this, ten years outcome of both groups LD was similar: none of LD developed ESRD, 9.8% of accepted and 11.8% of unaccepted LD died (p = .803). CONCLUSIONS: During an average of 101 months of follow-up mortality of accepted LD did not differ significantly as compared to the age standardized Serbian population and none of them developed ESRD. In examination of potential LD, the use of accurate and precise methods for kidney function estimation and the evaluation of risk for ESRD and mortality as well as treatment of modifiable contraindications for kidney donation are necessary.

Association between Hemodialysis Patient Outcomes and Compliance with KDOQI and KDIGO Targets for Mineral and Bone Metabolism.

BACKGROUND: Increased mortality of hemodialysis (HD) patients is associated with chronic kidney disease-mineral and bone disorders (CKD-MBD), and therefore, their correction may improve patient survival. Differences in targets recommended by KDOQI and KDIGO CKD-MBD guidelines directed us to compare the relative numbers of patients achieving these targets and to examine possible associations between compliance with the targets and patient outcome. METHODS: A total of 1,744 patients (61.2% males, aged 58.7 ± 12.5 years) dialyzed in 20 HD centers in Serbia were monitored for 3 years. The number of participants achieving KDOQI/KDIGO guideline targets for serum phosphorus, calcium, and iPTH was determined. The Cox proportional hazards model was used to select variables significantly associated with risk of time to death. RESULTS: A majority of patients were dialyzed thrice weekly for 4 h; 86.3% of them used phosphate binders and 49.3% vitamin D3. Proportions of patients achieving KDOQI and KDIGO targets were 49.5 and 44.4% for phosphorus, 53.2 and 76.7% for calcium, 21 and 42.8% for iPTH. Multivariate Cox analysis selected serum phosphorus level outside the KDIGO target, as well as serum iPTH levels outside KDOQI and KDIGO targets as significant mortality predictors. Areas under the receiver operating characteristic curves showed that achievement of both guideline targets for iPTH had similar survival predictive values. CONCLUSION: Serum phosphorus levels outside KDIGO targets and iPTH levels outside both KDOQI and KDIGO targets were associated with a significantly higher risk of death. These findings may be useful in the management of CKD-MBD and for establishing local guidelines.

Biomarkers of oxidative damage and antioxidant enzyme activities in pre-dialysis Balkan endemic nephropathy patients.

AIM: To obtain more insight into molecular mechanisms underlying oxidative stress in Balkan endemic nephropathy (BEN), biomarkers of oxidative stress and antioxidant enzyme activities were studied in 38 pre-dialysis BEN patients, 21 healthy BEN family members and 36 healthy subjects from non-endemic areas. METHODS: Protein thiol groups (P-SH), antioxidant enzyme activities [superoxide dismutase (SOD) and glutathione peroxidase (GPX)], were determined in plasma spectrophotometrically, while malondialdehyde adducts (MDA) by enzyme immunoassay. RESULTS: BEN patients had significantly lower plasma GPX activity in comparison with values for both control groups (p = 0.016), gradually decreasing with kidney function impairment estimated by glomerular filtration rate (r = 0.53, p = 0.002). GPX activity was inversely correlated with serum urea (r = -0.627, p < 0.001), creatinine (r = -0.53, p < 0.05), urinary excretion of protein and α1-microglobulin (r = -0.44, p = 0.012; r = -0.50, p < 0.007). Significant upregulation of SOD activity was observed in healthy BEN family members (p < 0.05). While the concentration of MDA adducts was similar in all three groups, BEN patients and healthy BEN family members exhibited increased protein damage, based on fewer P-SH groups in comparison with subjects from non-BEN areas (p = 0.085; p = 0.014, respectively). CONCLUSIONS: Based on our results on increased oxidative protein damage in both pre-dialysis BEN patients and healthy BEN family members, it can be speculated that individuals from BEN areas, in general, are chronically exposed to some prooxidant environmental compounds. Moreover, decrease in plasma GPX activity, as a consequence of impaired kidney function, could further affect oxidative status in BEN patients.

Prevalence and risk factors of vascular calcification in pre-dialysis patients with Balkan endemic nephropathy.

Introduction: Vascular calcifications (VC) are common in patients with chronic kidney disease and present one of manifestations of mineral and bone disorders in these patients. Objective: The aim of this pilot study was to examine the prevalence and risk factors of VC in pre-dialysis patients with Balkan endemic nephropathy (BEN) and other kidney diseases. Methods: The study involved 32 pre-dialysis patients, 15 with BEN and 17 with other kidney diseases. All the patients underwent an interview, objective examination, routine laboratory analyses and measurement of serum concentration of intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 [25(OH)D3] and osteopontin. VCs in iliac, femoral, radial, and digital arteries were evaluated and Adragao VC score was calculated. The samples of radial artery were collected during the first creation of an arteriovenous fistula, and expression of osteocalcin, bone morphogenic protein-2 osteopontin, and matrix Gla-protein in arterial wall were examined. Results: Patients with BEN were significantly older (71.1 ± 6.1 vs. 54.7 ± 11.1 years), but they had significantly lower systolic and mean blood pressure (95.7 ± 13.2 mmHg vs. 104.3 ± 7.4 mmHg) and lower serum concentration of phosphorus (1.32 ± 0.36 mmol/l vs. 1.65 ± 0.35 mmol/l) and cholesterol (4.3 ± 1.1 mmol/l vs. 5.2 ± 0.8 mmol/l) than patients with other kidney diseases. Mean VC score was significantly lower in patients with BEN than in those with other kidney diseases (2.8 ± 1.7 vs. 4.6 ± 1.8; p = 0.009), but expression of four examined proteins in arterial wall differed insignificantly between the two groups. VC score correlated significantly with serum concentrations of cholesterol, triglycerides (positively), and iPTH (negatively). Conclusion: Pre-dialysis BEN patients had a significantly lower mean score of VC than patients with other kidney diseases.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients.

OBJECTIVES: The aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. METHODS: A cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1-1.8mmol/L), calcium (2.1-2.4mmol/L) and iPTH (150-300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. RESULTS: The patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. CONCLUSION: Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

Achievement of guideline targets in elderly patients on hemodialysis: a multicenter study.

OBJECTIVES: Advanced age is associated with shorter survival on dialysis. The aim of the present study was to compare the adherence with KDOQI guideline targets and the association between mortality and satisfying the guidelines targets between hemodialysis patients aged 65 years and over and those younger than 65 years. METHODS: Data were collected using a questionnaire sent to all 46 HD centers in Serbia with totally 3868 HD patients. The 24 centers responded and sent the data on all patients aged 18 years or older that were on regular HD for more than 3 months (2153 patients, 1320 males, aged 18-90 years). Data are presented in two groups: a group of patients younger than 65 years (1438, 66.8 %) and a group of patients aged 65 years and over (715, 33.2 %). The percentage of patients whose values failed to meet the targets recommended by KDOQI Clinical Practice Guidelines was calculated for dialysis dose (spKt/V), hemoglobin, serum phosphorus, serum calcium and plasma iPTH (150-300 pg/mL). Patients were followed from enrollment until their death, kidney transplantation, departure from the center or the end of the study. RESULTS: Elderly patients were more likely to have hypertension, significantly lower systolic and diastolic blood pressure and smaller dialysis vintage than younger patients. They were less frequently treated with high-flux membranes and hemodiafiltration and they had significantly lower number of dialysis hours per week and significantly lower interdialytic weight gain. They used ESA and phosphate binders less frequently than younger patients (p < 0.001 and p = 0.002). Older patients had similar Kt/V as younger ones but they had significantly more frequent Hb level outside the target range than younger patients. During the year follow-up period, by using a Cox proportional hazards model it has been confirmed that age, dialysis vintage, weekly dialysis time and target values for Kt/V were significant independent predictors of time to death for younger patients and gender, dialysis vintage and iPTH were independent predictor of time to death for older patients. CONCLUSION: Despite less favorable dialysis prescription, older patients had similar Kt/V and less frequent deviations from the target values proposed by KDOQI for serum phosphorus and iPTH but more frequent deviation for Hb value as compared with younger patients. Risk factors for mortality differ between older and younger patients; out of five KDOQI targets, only Kt/V proved to be a significant risk factor for mortality for younger and iPTH for older patients.

Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report.

BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients ≥75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients ≥75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3-60.0) which fell to 39.3% (95% CI: 38.7-39.9) in patients 65-74 years and 21.3% (95% CI: 20.8-21.9) in patients ≥75 years.

Comprehensive geriatric assessment: comparison of elderly hemodialysis patients and primary care patients.

BACKGROUNDS: The quality of life and survival of elderly depend not only on their age but on many social and health factors. In the present study, comprehensive geriatric assessment (CGA) was made in elderly patients on regular hemodialysis (HD) and those without chronic kidney disease recruited in primary health care in order to compare their sociodemographic characteristics, physical health, functional ability and social support. METHOD: The 106 HD patients and 300 primary care patients aged 70 years and more were studied. Data on sociodemographic characteristics, neurosensory deficits, pain, falls, polypharmacy, basic activities of daily living (ADL) questionnaire, instrumental activities of daily living (IADL) questionnaire were obtained during interview. The Timed Up and Go, Nutritional Health Checklist, Two Question Instrument for depression and Charlson comorbidity index (CCI) were applied. RESULTS: No significant differences were found for age, gender, education level and dwelling between the two groups. A lower percentage of HD patients lived alone when compared with controls. BMI >25 kg/m(2) had 43.4% of HD patients and 49.3% of controls. CCI differed significantly between HD and primary care patients (median: 6 vs. 4) and significantly more HD patients reported depression. No significant difference was found between groups for cognitive dysfunction and ADL, but HD patients had significantly lower IADL scores than controls. The mobility of HD patients was worse; 45.7% of them reported falls in the previous year but only 9.7% from the controls. CONCLUSIONS: CGA revealed that HD patients had significantly higher CCI, worse IADL score, mobility and reported more frequent falls, depression and impaired vision than primary care patients.

Quality of diabetes care in family medicine practices in eastern Bosnia and Herzegovina.

OBJECTIVES: In the present study, the audit of medical files of patients with diabetes, followed in family medicine practices in the eastern region of Bosnia and Herzegovina (BiH), was carried out in order to investigate the frequency of the use of screening tests for early diagnosis of diabetes complications. METHODS: The audit was conducted in 32 family medicine practices from 12 primary health care centers in the eastern part of BiH over one-year period (March 2010 to March 2011). A specially established audit team randomly selected medical files of 20 patients with diabetes from the Diabetes Registry administered by each family medicine team database. Screening tests assessed are selected according to the ADA guidelines. RESULTS: Frequency of the individual screening test varied between 99%, found for at least one blood pressure measurement, and 3.8% for ABI measurement. When the frequency of optimal use of screening was analyzed, only 1% of patients received all recommended screening tests. CONCLUSION: The frequency of the use of screening tests for chronic diabetes complications was found to be low in the eastern part of Bosnia and Herzegovina. Multivariate linear regression analysis showed that longer duration of diabetes and a larger number of diabetics per practice were associated with a smaller number of screening tests, but specialists in family medicine provided a higher number of screening tests compared to other physicians.

Is increased susceptibility to Balkan endemic nephropathy in carriers of common GSTA1 (*A/*B) polymorphism linked with the catalytic role of GSTA1 in ochratoxin a biotransformation? Serbian case control study and in silico analysis.

Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates.

Renal replacement therapy in Europe: a summary of the 2011 ERA-EDTA Registry Annual Report.

BACKGROUND: This article provides a summary of the 2011 ERA-EDTA Registry Annual Report (available at www.era-edta-reg.org). METHODS: Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. From 27 registries, individual patient data were received, whereas 17 registries contributed data in aggregated form. We present the incidence and prevalence of RRT, and renal transplant rates in 2011. In addition, survival probabilities and expected remaining lifetimes were calculated for those registries providing individual patient data. RESULTS: The overall unadjusted incidence rate of RRT in 2011 among all registries reporting to the ERA-EDTA Registry was 117 per million population (pmp) (n = 71.631). Incidence rates varied from 24 pmp in Ukraine to 238 pmp in Turkey. The overall unadjusted prevalence of RRT for ESRD on 31 December 2011 was 692 pmp (n = 425 824). The highest prevalence was reported by Portugal (1662 pmp) and the lowest by Ukraine (131 pmp). Among all registries, a total of 22 814 renal transplantations were performed (37 pmp). The highest overall transplant rate was reported from Spain, Cantabria (81 pmp), whereas the highest rate of living donor transplants was reported from Turkey (39 pmp). For patients who started RRT between 2002 and 2006, the unadjusted 5-year patient survival on RRT was 46.8% [95% confidence interval (CI) 46.6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors.

20 years since the establishment of the BANTAO association (Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs).

The Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was born in Ohrid on October 9, 1993. The war in former Yugoslavia negatively affected the development of nephrology and also the connections among the nephrologists from the Balkans. However, there was willingness for further mutual collaboration between the nephrologists from the Balkans. The war in Yugoslavia created hate among people, between the newly established countries, and there were problems with the recognition of the names of the new countries, and so, the nephrologists decided to apply the ancient principle of using the names of the cities, instead of the countries, as the founders of the Association. The main goal of BANTAO is to promote scientific and technical cooperation in the fields of renal disease and artificial organs between the regions on the Balkan Peninsula and the world, to give an opportunity for exchange of experience and knowledge among the experts in the area and to engage in collaborative projects in order to demonstrate that cooperation is possible even on the turbulent Balkan Peninsula. The I BANTAO congress was held in Varna from September 22 to 24th, 1995 (President--D. Nenov, Varna). The II congress of BANTAO was held from September 6th to 10th, 1997 in Struga, (President--M. Polenakovic, Skopje). The III BANTAO congress was held in Belgrade from September 18th to 20th, 1998 (President--Lj. Djukanovic, Belgrade). The IV congress of BANTAO was held in Izmir from 14th to 16th November 1999 (President--A. Akcicek, Izmir). The V Congress of BANTAO was held in Thessaloniki from September 30th to October 3rd, 2001 (President--P. Stathakis, Athens). The VI Congress of BANTAO was held for the second time in Varna from 6th to 9th October 2003 (President--D. Nenov, Varna). The VII congress of BANTAO was held from September 8th to 11th, 2005 in Ohrid, (President--M. Polenakovic, Skopje). The VIII BANTAO congress was held in Belgrade, 16-19 September 2007 (President--V. Nesic, Belgrade). The IX BANTAO congress was held in Antalya, 18-22 November 2009 (President--A. Basci, Izmir). The X BANTAO congress was held from 13 to 15 October 2011 in Chalkidiki (President--D. Tsakiris, Thessaloniki). The XI BANTAO congress is being held on 26-29 September 2013 in Timisoara (President--A. Schiller, Timisoara). At the VII BANTAO Congress for the first time a CME Course was organized by ERA/EDTA and ISN/COMGAN entitled "Frontiers in Nephrology" with seven distinguished speakers. Very important event in the existence of BANTAO is the appearance of the BANTAO journal in 2003. The BANTAO journal has been published biannually since 2003. In the past 10 years, 20 regular issues; 2 supplements (Antalia and Chalkidiki congresses) have been published. Editors of the journal were as follows: 2003-2005--D. Nenov, Editor; 2005-2009--A. Basci, Editor; 2009--Goce Spasovski, Editor. Until now 332 papers have been published. The BANTAO journal is on EBSCO, DOAJ, SCOPUS. After the First Congress of BANTAO, F. Valderrábano, chairman of the EDTA--ERA Registry, at that time, wrote in Nephrology Dialysis Transplantation (1996) 11:740: "Nephrologists of the Balkan countries meet across political frontiers and war fronts--an example to politicians! BANTAO: a new European Medical Association overcomes Political obstacles." Despite the difficulties imposed by major events, such as devastating wars and catastrophic earthquakes in many countries of the Balkan Peninsula BANTAO has made considerable progress. The BANTAO Congress was established as the major scientific and institutional forum for Balkan nephrologists, with its own journal, indicating our will to communicate, to collaborate, to get to know each other and to share our difficulties. Now, we expect further successful work of BANTAO.

The pharmacokinetics of recombinant human erythropoietin in Balkan endemic nephropathy patients.

BACKGROUND: Balkan endemic nephropathy (BEN) hemodialysis patients require a higher dose of recombinant human erythropoietin for maintaining target hemoglobin level than patients with other kidney diseases. OBJECTIVES: Comparison of the pharmacokinetics of beta-erythropoietin given subcutaneously to hemodialysis patients with BEN or other kidney diseases (non-BEN). METHODS: Recombinant human erythropoietin (75 U/kg) was administered subcutaneously to 10 BEN and 14 non-BEN hemodialysis patients. The predose plasma level of erythropoietin (Epo) was subtracted from all postdose levels. The relevant pharmacokinetic parameters were calculated after noncompartmental pharmacokinetic analysis using Kinetica software (Thermo Scientific, ver.5.0). RESULTS: Although basal plasma Epo concentration was similar in BEN (20.1 ± 10.3 U/L) and non-BEN (15.1 ± 8.1 U/L; p=.1964) patients, there were significant differences between the groups for elimination rate constant (0.016 ± 0.006 vs 0.026 ± 0.011 hr⁻¹; p=.020) and elimination half-life (50.24 ± 19.12 vs 33.79 ± 18.91 hr, p=.048). These differences remained significant after adjustment for patient characteristics (age, sex, hemodialysis duration, ferritin, PTH and ACEI use). No significant differences between groups were found in maximal Epo concentration, time to maximum Epo concentration, area under the curve from time of dosing extrapolated to infinity, clearance, mean residence time of Epo between groups both before and after adjustment. CONCLUSION: Pharmacokinetic analysis of beta-erythropoietin detected a significantly longer elimination half-life in BEN than in non BEN patients. This finding needs to be confirmed in a well-controlled study with a larger sample size.