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.

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.

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.

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.

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.

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.

Trends in incidence and prevalence of Balkan endemic nephropathy in the three most affected villages in Serbia over a 36-year period.

The study was undertaken with the aim to evaluate trends in incidence and prevalence of Balkan endemic nephropathy (BEN) in the villages Sopic, Petka, and Vreoci, Lazarevac municipality, Serbia. Data concerning BEN notifications in the population-based registry of the Special Hospital for Endemic Nephropathy, Lazarevac were used to evaluate BEN incidence rates in the three villages over the period 1973-2008. Population estimates were based on national census data. All age-adjusted incidence rates were standardized to the European standard population and trends were assessed by Poisson regression model and joinpoint analysis. The prevalence of BEN was obtained in cross-sectional studies carried out in the villages Sopic (1971 and 1992), Vreoci (1971 and 2002), and Petka (1971 and 2008). The overall age-standardized incidence rates of BEN in the three villages changed over time. The significant 8.6% annual decrease in the first 16 years of the observed period was followed by a slight increase of 4.6% annually in the last two decades. The age-standardized incidence rates changed over time, being the greatest in the years when the field investigations were made. There was an insignificant change in BEN prevalence in Sopic and Vreoci and a significant decrease in prevalence in Petka. During a 36-year period, 367 new cases of BEN were registered in the three endemic villages and the overall age-standardized incidence rate varied over time. As BEN is a slow-progressing and asymptomatic chronic kidney disease, early detection of BEN can only be achieved by field examination.

Screening of elderly for chronic kidney disease.

BACKGROUND AND AIMS: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years--one without and the other with hypertension. METHODS: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertension. Data on patients were obtained by interview, analysis of medical records and physical examinations. Serum and urine creatinine, proteinuria, microalbuminuria (MAU, turbidimetry), and urinary sediment were analyzed. RESULTS: Among the 585 patients, there were 54.5% with a positive family history for hypertension and 14% for kidney diseases. MAU was significantly more frequent (30 vs. 11%) and the mean estimated glomerular filtration rate (eGFR) higher (71 ± 14 vs. 64 ± 14 ml/min/1.73 m) in patients without hypertension than in those with hypertension. The majority of patients with stage 3 CKD had eGFR >45 ml/min/1.73 m(2) with normal urinary findings. Multivariate logistic regression analysis found age and treatment with angiotensin-converting enzyme inhibitors to be associated with reduced eGFR, MAU and proteinuria. In addition, smoking was associated with eGFR, but a family history for kidney disease and belonging to the group without hypertension were associated with MAU. CONCLUSION: The high prevalence of markers for CKD in symptomless elderly without hypertension confirmed that the elderly, as a high-risk population, should be screened based on increased age alone.

High prevalence of risk factors for chronic kidney disease in Balkan endemic nephropathy foci.

BACKGROUND/AIMS: The aim of this study was to find out the prevalence of the most frequent risk factors for chronic kidney disease (CKD) and the prevalence of urinary abnormalities in adult inhabitants of three Balkan endemic nephropathy (BEN) villages near Bijeljina, Bosnia and Herzegovina. METHODS: The survey consisted of an interview, blood pressure measurement, and urine dipstick test for proteinuria, hematuria, and glycosuria. RESULTS: The study involved 1625 (739 males, aged 51 ± 16 years) subjects: 319 (19.6%) with positive family history for BEN, 585 (36%) with hypertension, 604 (37.2%) above 60 years, 146 (9%) with diabetes, and 566 (34.8%) with none of these risk factors. Proteinuria was present in 6.2-7.1% of the subjects with risk factors for CKD but in 3.4% of those without risk factors. Systolic blood pressure and BEN in brother/sister were found to be significant variables associated with proteinuria, but female gender and history of kidney disease with hematuria. CONCLUSION: In addition to a family burden for BEN, other risk factors for CKD were highly prevalent in BEN villages of the Bijeljina municipality. The frequency of proteinuria was higher in the at-risk group than in the group without risk factors and increased with the number of risk factors.

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.

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.

The predictive value of anthropometric parameters on mortality in haemodialysis patients.

BACKGROUND: Since protein-calorie malnutrition is a common factor influencing morbidity and mortality of haemodialysis patients, assessing their nutritional status is important. The aim of this study was to investigate the predictive value of anthropometric parameters on mortality and their interrelationship. METHODS: The study included a cohort of 242 patients. The analysis involved baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and included skinfolds, mid-arm circumference (MAC), body height and weight. The percentage of body fat (%fat) was calculated from triceps (TSF), biceps, subscapular and suprailiac skinfolds (Disease Outcomes Quality Initiative (DOQI) guidelines) and mid-arm muscle circumference (MAMC) from MAC and TSF. Body mass index (BMI), Kt/V, normalized protein catabolic rate (NPCR) and cardiovascular co-morbidity were also determined and laboratory analyses undertaken. RESULTS: Strong correlations were found among the anthropometric parameters. Extended Cox regression analysis selected %fat, MAC, MAMC and TSF in addition to age, ischaemic heart disease, congestive heart failure, Kt/V, haemoglobin, creatinine, albumin and NPCR as potential predictors of mortality. The same anthropometric parameters were found to be independent mortality predictors in corresponding models. The most predictive anthropometric factor was MAC. BMI was not a risk factor. CONCLUSION: Percentage of body fat, MAC, MAMC and TSF were independent predictors of mortality of haemodialysis patients, and MAC was the most predictive one.

Time trends in Balkan endemic nephropathy incidence in the most affected region in Serbia, 1977-2009: the disease has not yet disappeared.

BACKGROUND: Balkan endemic nephropathy (BEN) is a familial chronic kidney disease, which occurs only in some regions of the Balkan Peninsula. The aim of this study was to determine the main epidemiological features of BEN in the Kolubara region, the most affected region in Serbia, and to try to elucidate the controversial issue of whether or not BEN is tapering off. METHODS: To evaluate the BEN incidence rates in the municipality of Lazarevac over a 33-year period (1977-2009), we used data of BEN notifications from the BEN Registry located in the Special Hospital for Endemic Nephropathy, Lazarevac. Population data were obtained from the 1981, 1991 and 2002 national censuses by interpolation. BEN incidence rates were standardized according to the European standard population, and their trends were assessed by Poisson regression model and joinpoint analysis. RESULTS: The age-adjusted BEN incidence rates combined for both sexes over a 33-year period (1977-2009) fitted a significant quadratic (U-shaped) trend (y = 58.44 - 3.76 + 0.10x(2), P = 0.026). Joinpoint analysis showed that the overall age-standardized BEN incidence rates significantly decreased in the first decade of the observed period (1977-89) by an average of 10.0% annually, while a nonsignificant increase of 3.9% per year was recorded in the last two decades (1989-2009). CONCLUSIONS: Our results revealed that BEN still exists in the Kolubara region. The predicted disappearing scenario of this still mysterious disease has not happened.

Beneficial effects of donor-specific transfusion on renal allograft outcome.

INTRODUCTION: Donor-specific transfusion (DST) is claimed to improve graft survival in living kidney transplantation. The aim of this study was to determine the influence of DST on the incidence of acute rejection (AR), graft function and survival in the early and late post-transplantation period in transfusion-naïve patients. METHODS: Three patient groups were compared: group 1 received DST (n = 18), group 2 patients received no transfusion prior to surgery (n = 13) and group 3 consisted of 132 randomly transfused patients. The DST protocol consisted of infusion of fresh whole donor blood (3 × 150 mL) at two-wk intervals accompanied by three d of azathioprine. All patients were grafted within one month after the third DST. Triple drug immunosuppression based on cyclosporine A was given to all patients. RESULTS: DST and polytransfused patients experienced significantly less AR compared with group 2 patients. Two-yr graft function was significantly better in patients in groups 1 and 3 compared with group 2. Although similar eight-yr patient and graft survival was found in all the groups, delayed graft function patients had the longest graft half-life. CONCLUSION: DST imposes a significant beneficial effect on the incidence of AR, DGF and graft function during the first post-transplantation year in transfusion-naïve patients receiving standard immunosuppression therapy.

Beta2-microglobulin and alpha1-microglobulin as markers of Balkan endemic nephropathy, a worldwide disease.

BACKGROUND: Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined. METHODS: This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families. RESULTS: In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker. CONCLUSION: All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.

High prevalence of kidney disease in two rural communities in Kosovo and Metohia.

A systematic survey was carried out in an enclave in Kosovo and Metohia, with the aim of assessing the prevalence of kidney diseases. The survey involved 423 (180 males) adult inhabitants from two small settlements, Velika Hoca and Orahovac, and included an interview, medical documentation, physical, ultrasound, and laboratory examinations. Persons with any detected disorder indicating kidney disease were invited for additional examination of kidney function. Using urine dipstick test, proteinuria was detected in 19.1% and hemoglobinuria in 4.5% of the examined subjects. Glomerular filtration rate (Modification of Diet in Renal Disease (MDRD) formula) below 60 mL/min/1.73 m(2) was found in 5.2% of subjects. Kidney ultrasound examination detected reduced length of right and left kidneys in 38 and 24 persons, respectively. Cysts were also a frequent finding, but polycystic kidney, hydronephrosis, and kidney stones were found in about 2% each. The analysis of data obtained by the present examination and available medical documentation revealed kidney and urinary tract diseases in 98 persons: 52 patients with already known disease and 46 patients detected in the survey. Out of them in 22 patients diagnosis of kidney disease could not be established during the survey but laboratory analyses indicated that they might suffer from tubulointerstitial disease: 14 had tubular dysfunctions, 8 of them low-grade proteinuria, and 12 had a positive family history for kidney disease. In the enclave of Velika Hoca and Orahovac the prevalence of kidney disease was 7.0% indicating that these communities might be placed among those with a high prevalence of kidney disease in Serbia.

Screening of chronic diseases and chronic disease risk factors in two rural communities in Kosovo.

BACKGROUND: A cross-sectional study was carried out in Velika Hoca and Orahovac, two rural communities in Kosovo and Metohia, with the aim of assessing the prevalence of chronic diseases and associated risk factors. METHODS: The study involved 423 (180 male) adult inhabitants aged 51 +/- 16 years and included an interview, medical documentation, physical, ultrasound, laboratory examinations and ECG. RESULTS: Hyperlipidemia was the most frequent (70%) risk factor followed by alcohol consumption (47%), hypertension (42%), smoking (36%) and obesity (32%). Ischemic heart disease was diagnosed in 25 patients, hypertensive cardiomyopathy in 17, other cardiomyopathies in 5 and arrhythmia in 20 patients. Nine persons had chronic obstructive pulmonary disease. Previously diagnosed liver cirrhosis occurred in 5 and chronic hepatitis in 8 subjects, while liver steatosis with elevated serum transaminases (22 persons), elevated transaminases with normal ultrasound (20 persons), tumor or suspected tumor (7 persons) were detected in the survey. Gastrointestinal symptoms were the most prevalent but peptic ulcer and gastritis had been previously diagnosed in 64 and 47 patients. Kidney and urinary tract diseases were known for 52 patients (12 with chronic renal failure and 4 on hemodialysis) and 46 more were detected in the study. Among them in 22 patients with markers of kidney disease and unclear diagnosis 12 had a positive family history, 8 low-grade proteinuria, 14 tubular dysfunctions and 7 eGFR (estimated glomerular filtration rate) below 60 ml/min/1.73 m2. CONCLUSION: In the Serbian enclave of Velika HoEa and Orahovac the prevalence of cardiovascular diseases was similar to that of gastrointestinal, liver and kidney diseases. This differs from other parts of Serbia where cardiovascular disorders are the leading cause of disease burden.

Health-related quality of life, treatment efficacy, and hemodialysis patient outcome.

The aim of the study was to examine the influence of improved treatment of hemodialysis (HD) patients on their health-related quality of life (HrQoL) and to assess the predictive value of HrQoL dimensions on patient outcome. The prospective cohort study involved 102 HD patients, and their clinical and laboratory parameters and HD adequacy indices were followed from 2001 to 2007. HrQoL was measured using KDQOL-SF Version 1.3 in 2001, 2004, and 2007. During a six-year period, quality of HD and anemia treatment improved and resulted in significant increase of mean Kt/V (1.2-1.56) and hemoglobin levels (86.5-115.6 g/L). All four HrQoL dimensions (i.e., physical, mental health, kidney disease target issues, and patient satisfaction) remained unchanged, but significant improvement in several HrQoL physical health domains and the effects of kidney disease domain was found. Mortality rate decreased from 18.6% to 7.14% per year. Age was associated positively, but kidney disease target issue score negatively, with patient death. Improved HD adequacy and anemia treatment in HD patients were followed with maintenance of all four HrQoL dimensions unchanged over six years. Moreover, an improvement in several physical health domains and the effects of kidney disease domain was found. Age and kidney disease target issue appeared as significant predictors of patients' death.

Contribution to the definition of diagnostic criteria for Balkan endemic nephropathy.

BACKGROUND: Diagnostic criteria for Balkan endemic nephropathy (BEN) have not been precisely established. In the present study the predictive value of variables previously proposed as diagnostic criteria for BEN was examined. METHODS: The study involved 182 patients: 98 patients with BEN, 57 patients with other kidney diseases (20 with glomerulonephritis, 17 with tubulointerstitial diseases and 20 with hypertensive nephrosclerosis) and 27 healthy subjects. The BEN group comprised patients who fulfilled criteria for BEN and suspected BEN, together with patients with proteinuria and at least two tubular abnormalities or one tubular abnormality and a history of urothelial tumour. Demographic, clinical, laboratory and ultrasound variables of examined groups were combined in univariate/multivariate logistic regression analysis. RESULTS: Out of 28 analysed variables only urine alpha1-microglobulin (MG) and kidney length were selected as significant predictors in differentiating BEN from other kidney diseases and healthy controls. Using ROC curves the cutoff values of these variables and proteinuria and kidney volume, variables collinear with them, were found. Moderate sensitivity and specificity characterized all these cutoff values except for proteinuria, which provided high sensitivity and specificity in combination of BEN and healthy persons. The predictive value of different combinations of selected variables was not significantly different from the predictive value of each variable individually. CONCLUSIONS: Proteinuria, urine alpha1-MG, kidney length and volume were selected as significant predictors of BEN. Variables related to kidney failure as well as several tubular disorders (urine specific gravity, FENa and TRP) had an insignificant predictive value and could not be used for differential diagnosis of BEN.