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Balkan endemic nephropathy (BEN) presents an unsolved puzzle despite fifty years of its investigation. Academy of Medical Sciences of the Serbian Medical Society organized a round table discussion on current unsolved problems related to BEN. The present paper summarizes presentations, discussion and conclusions of this meeting. During the last fifty years, the course of BEN prolonged and it shifted towards the older age in all endemic foci. Data on the incidence of BEN have been controversial and frequently based on the data on the number of BEN patients starting haemodialysis treatment. In Serbia, BEN patients present 6.5% of haemodialysis population and this percentage differs among different centres ranging from 5% (Leskovac) to 46% (Lazarevac). Maintenance of high prevalence of BEN patients on regular haemodialysis indicates that BEN is not an expiring disease. In addition, recent data have shown more frequent microalbuminuria and low-molecular weight proteinuria in children from endemic than from nonendemic families. Aetiology of BEN is still unknown despite numerous investigations of environmental and genetic factors. Today, there is a very current hypothesis on the aetiological role of aristolochic acid but the role of viruses, geochemical factors and genetic factors must not be neglected. Morphological features of BEN are nonspecific and characterized by acellular interstitial fibrosis, tubular atrophy and changes on preand postglomerular vessels. New immunohistochemical and molecular biology methods offer a new approach to BEN investigation. Association of BEN with high incidence of upperurothelial tumours is well-known. Recent studies have shown significant changes of demographic characteristics of patients suffering upper-urothelial tumours, their prevalence in different endemic foci and characteristics of tumours. Further studies of BEN should be directed to determination of incidence and prevalence of disease in different endemic foci, investigations of different insufficiently examined aetiological factors as well as pathomorphological features of the disease by the use of modern methods.

Background/Aim. Hemodialysis (HD) is a therapeutic procedure used to partially correct homeostatic disorders and prevent complications of uremia to appear in the terminal stage of renal insufficiency. The aim of this study was to evaluate and analyze the incidence and features of headaches in patients undergoing hemodialysis. Methods. A total of 143 patients, 50 women and 93 men, undergoing hemodialysis, were questioned about their problems with headache using a questionnaire designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. The patients were separated into two groups: the patients without headache and the patients with repeated headaches. Afterwards, the patients with headaches were further divided into subgroups: the patients who had the headaches before the beginning of HD and patients who experienced repeated headaches with the beginning of HD headache (HDH). In the group of patients with headaches we analyzed characteristics of headache according to which diagnoses of headaches were made, as well as the effects of HD on headaches. We also analyzed features of HDH. The patients with headache were compared to the patients without headache regarding sex, age, duration of HD, causes of end-stage renal disease, arterial diastolic and systolic blood pressure and serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The results were statistically compared. Results. In the group of 143 patients examined, 27 (18.9%) patients had headaches. There were no statistically significant differences between the group of patients with headaches and those without headache regarding to sex, age, duration of HD, causes of end-stage renal disease, serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The patients with headaches showed significantly higher mean values of systolic blood pressure during HD in comparison to the patients without headaches (p = 0.029). There was no statistically significant difference between the two groups regarding the mean values of diastolic blood pressure. Nineteen (13.3%) patients had had headache before starting HD. HD did not have any effect on the characteristics of headaches in more than a half of these patients. In 8 (5.6%) patients we diagnosed HDH using the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. HDH showed similar characteristics in all the patients: it appeared mostly in men, during the 4th hour of HD, lasted less than four hours, it was localized bilaterally in the frontal parts of the head, strong in intensity, throbbing and without the associated symptoms. Conclusion. The results of our study clearly showed that HDH was a particular entity of headache, not only because of its connection with HD, but because it had similar characteristics in all the patients in which it had appeared. Finding out the pathophysiological mechanisms of their occurrence would significantly improve the quality of life style of patients on hemodialysis. .

Background/Aim: The aim of this study was to compare plasma and urine transforming growth factor-β1 (TGF-β1) levels in patients with different stages of Balkan endemic nephropathy (BEN) with those in patients with primary glomerulonephritis (GN) and healthy controls. Methods: The study involved 47 patients with BEN (30 with manifest BEN and 17 in the early stage of BEN), 12 patients with GN and 10 healthy controls. Plasma and urine TGF-β1 was assayed by enzyme-linked immunosorbent assay. Results: The median plasma TGF-β1 levels differed nonsignificantly between the groups (4,908–6,442 pg/ml), but individual plasma TGF-β1 levels in BEN patients exhibited the highest dispersion. Median urinary TGF-β1 excretion (pg/mg creatinine) was significantly higher in patient groups (manifest BEN: 203, early-stage BEN: 341, GN: 775) than in healthy controls (42). No correlation was found between plasma and urine TGF-β1 levels or between plasma TGF-β1 levels and creatinine clearance for any of the examined groups. Conclusion: Plasma TGF-β1 levels in BEN patients extended over the widest range, but no significant differences were found between the median values for the groups. Median urinary TGF-β1 excretion was significantly higher in patients with BEN and GN than in healthy controls. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the relationship between kidney dimensions and creatinine clearance (Ccr) in patients with Balkan endemic nephropathy (BEN), nephrosclerosis (NSc), glomerulonephritis (GN), diabetic nephropathy (DN) and in healthy persons. The main objective was to find out at which stage of BEN the kidneys start to shrink. Methods: The study involved 84 patients with BEN, 39 with NSc, 56 with GN, 55 with DN, and 52 healthy subjects, allocated to group 1 (n = 28) sex- and age-matched with BEN/NSc patients, or group 2 (n = 24) sex- and age-matched with GN/DN patients. Based on Ccr, patients were classified according to the NKF/DOQI guidelines. Results: The kidney dimensions of BEN patients in all stages of the disease were significantly shorter than those of healthy controls and patients with GN and DN. In stages 3–5, BEN patients had significantly smaller kidneys than patients with NSc. Patients with NSc had smaller kidney dimensions than controls and GN/DN patients but all of these differences were not significant. Conclusion: BEN patients had significantly smaller kidneys than sex- and age-matched healthy persons and patients with GN and DN in all stages of the disease and patients with NSc in stages 3–5 of the disease. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aim. Hemodialysis (HD) is a therapeutic procedure used to partially correct homeostatic disorders and prevent complications of uremia to appear in the terminal stage of renal insufficiency. The aim of this study was to evaluate and analyze the incidence and features of haedaches in patients undergoing hemodialysis. Methods. A total of 143 patients, 50 women and 93 men, undergoing hemodialysis, were questionned about their problems with headache using a questionnary designend according to the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. The patients were separated into two groups: the patients without headache and the patients with repeated headaches. Afterwards, the patients with headaches were further divided into subgroups: the patients who had the headaches before the beginning of HD and patients who experienced repeated headaches with the beginning of HD headache (HDH). In the group of patients with headaches we analyzed characteristics of headache according to which diagnoses of headaches were made, as well as the effects of HD on headaches. We also analyzed features of HDH. The patients with headache were compared to the patients without haedache regarding sex, age, duration of HD, causes of end-stage renal disease, arterial diastolic and systolic blood pressure and serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The results were statistically compared. Results. In the group of 143 patients examined, 27 (18.9%) patients had headaches. There were no statistically significant differences between the group of patients with headaches and those without headache regarding to sex, age, duration of HD, causes of end-stage renal disease, serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The patients with headaches showed significantlly higher mean values of systolic blood pressure during HD in comparison to the patients without headaches (p = 0.029). There was no statistically significant difference between the two groups regarding the mean values of diastolic blood pressure. Nineteen (13.3%) patients had had headache before starting HD. HD did not have any effect on the characteristics of headaches in more than a half of these patients. In 8 (5.6%) patients we diagnozed HDH using the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. HDH showed similar caracteristics in all the patients: it appeared mostly in men, during the 4th hour of HD, lasted less than four hours, it was localized bilaterally in the frontal parts of the head, strong in intensity, throbbing and without the associated symptoms. Conclusion. The results of our study clearly showed that HDH was a particular entity of headache, not only because of its connenction with HD, but because it had similar characteristics in all the patients in wich it had appeared. Finding out the pathophysiological mechanisms of their occurrence would significantly improve the quality of life style of patients on hemodialysis. [ABSTRACT FROM AUTHOR]

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.

Balkan endemic nephropathy (BEN) presents an unsolved puzzle despite fifty years of its investigation. Academy of Medical Sciences of the Serbian Medical Society organized a round table discussion on current unsolved problems related to BEN. The present paper summarizes presentations, discussion and conclusions of this meeting. During the last fifty years, the course of BEN prolonged and it shifted towards the older age in all endemic foci. Data on the incidence of BEN have been controversial and frequently based on the data on the number of BEN patients starting haemodialysis treatment. In Serbia, BEN patients present 6.5% of haemodialysis population and this percentage differs among different centres ranging from 5% (Leskovac) to 46% (Lazarevac). Maintenance of high prevalence of BEN patients on regular haemodialysis indicates that BEN is not an expiring disease. In addition, recent data have shown more frequent microalbuminuria and low-molecular weight proteinuria in children from endemic than from nonendemic families. Aetiology of BEN is still unknown despite numerous investigations of environmental and genetic factors. Today, there is a very current hypothesis on the aetiological role of aristolochic acid but the role of viruses, geochemical factors and genetic factors must not be neglected. Morphological features of BEN are nonspecific and characterized by acellular interstitial fibrosis, tubular atrophy and changes on pre- and postglomerular vessels. New immunohistochemical and molecular biology methods offer a new approach to BEN investigation. Association of BEN with high incidence of upper-urothelial tumours is well-known. Recent studies have shown significant changes of demographic characteristics of patients suffering upper-urothelial tumours, their prevalence in different endemic foci and characteristics of tumours. Further studies of BEN should be directed to determination of incidence and prevalence of disease in different endemic foci, investigations of different insufficiently examined aetiological factors as well as pathomorphological features of the disease by the use of modern methods.

Background/aim: Hemodialysis (HD) is a therapeutic procedure used to partially correct homeostatic disorders and prevent complications of uremia to appear in the terminal stage of renal insufficiency. The aim of this study was to evaluate and analyze the incidence and features of haedaches in patients undergoing hemodialysis., Methods: A total of 143 patients, 50 women and 93 men, undergoing hemodialysis, were questionned about their problems with headache using a questionnary designend according to the diagnostic criteria of the Intemational Headache Classification of Headache Disorders from 2004. The patients were separated into two groups: the patients without headache and the patients with repeated headaches. Afterwards, the patients with headaches were further divided into subgroups: the patients who had the headaches before the beginning of HD and patients who experienced repeated headaches with the beginning of HD headache (HDH). In the group of patients with headaches we analyzed characteristics of headache according to which diagnoses of headaches were made, as well as the effects of HD on headaches. We also analyzed features of HDH. The patients with headache were compared to the patients without haedache regarding sex, age, duration of HD, causes of end-stage renal disease, arterial diastolic and systolic blood pressure and serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The results were statistically compared., Results: In the group of 143 patients examined, 27 (18.9%) patients had headaches. There were no statistically significant differences between the group of patients with headaches and those without headache regarding to sex, age, duration of HD, causes of end-stage renal disease, serum concentration of hemoglobin, urea nitrogen, creatinine, sodium and potassium. The patients with headaches showed significantlly higher mean values of systolic blood pressure during HD in comparison to the patients without headaches (p = 0.029). There was no statistically significant difference between the two groups regarding the mean values of diastolic blood pressure. Nineteen (13.3%) patients had had headache before starting HD. HD did not have any effect on the characteristics of headaches in more than a half of these patients. In 8 (5.6%) patients we diagnozed HDH using the diagnostic criteria of the International Headache Classification of Headache Disorders from 2004. HDH showed similar caracteristics in all the patients: it appeared mostly in men, during the 4th hour of HD, lasted less than four hours, it was localized bilaterally in the frontal parts of the head, strong in intensity, throbbing and without the associated symptoms., Conclusion: The results of our study clearly showed that HDH was a particular entity of headache, not only because of its connenction with HD, but because it had similar characteristics in all the patients in wich it had appeared. Finding out the pathophysiological mechanisms of their occurrence would significantly improve the quality of life style of patients on hemodialysis.