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.

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

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.

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.

Screening of a population at risk of chronic kidney disease: analysis of factors associated with low eGFR and microalbuminuria.

BACKGROUND AND OBJECTIVE: Numerous screenings of chronic kidney disease (CKD) have been performed all over the world. This screening study was undertaken with the aim of estimating the prevalence of low glomerular filtration rate (eGFR) and microalbuminuria (MAU) and/or proteinuria in a population at risk for CKD and to detect factors associated with these CKD markers. MATERIALS AND METHODS: This cross-sectional study included 1617 patients without previously known kidney disease who came for regular check-ups to their general practitioners in 13 Belgrade health centers over a 3-month period. Patients selected were as follows: 1316 with hypertension, 208 with type 2 diabetes, and 93 older than 60 years without hypertension or diabetes. Screening included a questionnaire, blood pressure measurement, single MAU dipstick measurement (Micral-test® strip) and proteinuria and GFR estimation by Modification of Diet in Renal Disease. RESULTS: MAU was found in 419 (25.9%) patients, proteinuria in 163 (10.1%), and eGFR < 60 mL/min/1.73 m(2) in 370 (22.9%). Multivariate logistic regression analysis revealed that female gender, age, duration of hypertension, and smoking were associated with eGFR. Male gender, hypertension, treatment with angiotensin-converting enzyme inhibitors, proteinuria, and systolic blood pressure were associated with MAU. CONCLUSIONS: High prevalence of MAU/proteinuria and reduced eGFR were found in high-risk persons for CKD. Besides nonmodifiable, significant modifiable factors for MAU were use of angiotensin-converting enzyme inhibitors and strict regulation of hypertension and the factor for reduced eGFR was smoking.

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.

Transforming growth factor-beta 1 in Balkan endemic nephropathy.

BACKGROUND/AIM: The aim of this study was to compare plasma and urine transforming growth factor-beta1 (TGF-beta1) 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-beta1 was assayed by enzyme-linked immunosorbent assay. RESULTS: The median plasma TGF-beta1 levels differed nonsignificantly between the groups (4,908-6,442 pg/ml), but individual plasma TGF-beta1 levels in BEN patients exhibited the highest dispersion. Median urinary TGF-beta1 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-beta1 levels or between plasma TGF-beta1 levels and creatinine clearance for any of the examined groups. CONCLUSION: Plasma TGF-beta1 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-beta1 excretion was significantly higher in patients with BEN and GN than in healthy controls.

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.

Comparison of kidney size between patients with Balkan endemic nephropathy and other kidney diseases.

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.

Urinary protein patterns in patients with Balkan endemic nephropathy.

PURPOSE: Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls. METHODS: The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN. RESULTS: In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m(2) isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m(2), beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m(2) 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m(2) only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent. CONCLUSION: Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m(2). IgG was increasingly found as eGFR decreased.

Early detection of chronic kidney disease: collaboration of Belgrade nephrologists and primary care physicians.

BACKGROUND: Belgrade screening study was undertaken in order to detect persons with CKD markers in at risk populations and to educate primary care physicians how to carry out CKD screening. METHODS: The study was performed by primary care physicians from thirteen Belgrade health centers in collaboration with nephrologists from clinical centers. Subjects without previously known kidney disease were enrolled: 1316 patients with hypertension without diabetes, 208 patients with type 2 diabetes and 93 subjects older than 60 years without hypertension or diabetes. The survey consisted of an interview, consisted of an interview, estimation of glomerular filtration rate (eGFR-MDRD), single urine dipstick detection of proteinuria, hematuria, glucosuria, microalbuminuria. RESULTS: Microalbuminuria with or without proteinuria in combination with eGFR>60 ml/min/1.73 m2 was detected in 17% , 41% and 24% of patients with hypertension, diabetes and those above 60 years, respectively. Reduced eGFR (<60 ml/min/1.73 m2 ) was found in 23%, 12% and 22% of the same patient groups. The prevalence of CKD markers increased with increasing number of risk factors. CONCLUSION: High prevalence of CKD markers in at risk population detected by primary care physicians in this collaborative study seems to be the best way to encourage primary care physicians to carry out regular CKD screening.

[Investigation of Balkan endemic nephropathy in Serbia: how to proceed?].

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.

[One-year follow-up of renal function in endemic nephropathy families].

INTRODUCTION: Endemic nephropathy is familial, chronic tubulointerstitial disease with an insidious onset and asymptomatic, slow progressive course. OBJECTIVE: The present study was undertaken with the aim to find out whether new persons with renal disorders can be detected among members of endemic families in the village of Sopic (Kolubara River region, Serbia). METHODS: The study involved 44 members of five endemic families without history of renal disorders. Objective survey and laboratory analyzes that enabled determination of kidney functions (creatinine clearance, proteinuria, urine specific gravity and osmolality, fractional sodium excretion (FENa), the rate of tubular phosphate reabsorption (TRP), urine N-acetil-D-glycosaminidase and intestinal alkaline phosphatase) were done in all examined persons three times during the 6-month intervals. RESULTS: At the first examination, hypertension was detected in 23 (52%) person, decreased creatinine clearance in two and proteinuria in 10 persons included in the study. In addition, proteinuria and tubular disorders were detected in 6, hypertension, proteinuria and/or tubular disorders in 9 persons. The analysis of the results obtained by three check-ups undertaken during one year showed that proteinuria and tubular disorders appeared intermittently in half of the examined endemic family members. All persons with detected renal disorders required further examination in order to establish accurate diagnosis of renal disease. CONCLUSION: Three check-ups performed at six-month intervals in the members of five endemic families detected various renal disorders including renal hypofunction. Regular systematic check-ups of endemic families could enable early detection of the disease and early initiation of measures for slowing down chronic renal disease progression.

Evaluation of criteria for the diagnosis of Balkan endemic nephropathy.

BACKGROUND: The diagnosis of Balkan endemic nephropathy (BEN) is often made using Danilovic's criteria. The aim of this study was to determine the prevalence, sensitivity, specificity, and predictive value of Danilovic's criteria and several additional indices. METHODS: The study included 19 BEN patients, 23 BEN-suspected patients, 34 patients with other kidney diseases, and 23 healthy controls. The sensitivity and specificity of Danilovic's criteria was calculated, and these criteria, in addition to age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume, were combined in a logistic regression. RESULTS: All examined persons were from a BEN-affected village (criterion 1), and all BEN, BEN-suspected patients, and 12/23 healthy controls were from BEN families (criterion 2). None of the remaining Danilovic's criteria was found in the healthy controls. The prevalence of proteinuria, low specific gravity, and anemia (criteria 3-5) differed insignificantly among the patient groups. Azotemia and shrunken kidney (criteria 6 and 7) were significantly more frequent in BEN than in other patients. Only proteinuria showed high sensitivity and specificity in differentiating BEN and BEN-suspected patients from healthy persons, but no criteria differentiated BEN or BEN-suspected from other kidney diseases. Proteinuria is a significant predictor of both BEN and BEN-suspected vs. healthy persons, and alpha 1-microglobulinuria is a significant predictor of BEN vs. other kidney diseases. CONCLUSION: Danilovic's criteria enabled a diagnosis of BEN only in chronic renal failure and differential diagnosis between BEN and healthy persons but not between BEN and other kidney diseases. Out of the examined indices of proximal tubular disorders, only alpha 1-microglobulinuria significantly discriminated BEN from other kidney diseases.

Prevalence of Balkan endemic nephropathy has not changed since 1971 in the Kolubara region in Serbia.

BACKGROUND/AIMS: Thirty-one years after the first cross-sectional study, the population of Vreoci, a Balkan endemic nephropathy (BEN) village, was reinvestigated in order to determine the current prevalence of BEN and the clinical and laboratory characteristics of BEN family members with detected signs of kidney disease. METHODS: A total of 2,009 inhabitants (82% of the adult population) of the village were examined. Danilovic's criteria were used for diagnosis and classification of BEN. RESULTS: The prevalence of BEN (1.70%) was similar to that in 1971 (1.67%). Diagnosis of BEN was established in 19 BEN family members, suspected BEN in 23, proteinuria in 29, while 16 healthy members were examined as controls. Urine protein, alpha1-microglobulin levels and frequency of glucosuria were significantly higher and kidney length significantly smaller in the three patient groups than in healthy persons. Serum urea and creatinine levels were significantly higher, but creatinine clearance was lower in BEN and BEN suspected patients than in the other two groups. CONCLUSION: The prevalence of BEN remains stable over time in Vreoci village. Manifested disease was found in both BEN and BEN suspected patients. In persons with proteinuria but not enough criteria for BEN, tubular disorders and hypertension were frequently found.

Early detection of chronic kidney disease: Collaboration of Belgrade nephrologists and primary care physicians

Background: Belgrade screening study was undertaken in order to detect persons with CKD markers in at risk populations and to educate primary care physicians how to carry out CKD screening. Methods: The study was performed by primary care physicians from thirteen Belgrade health centers in collaboration with nephrologists from clinical centers. Subjects without previously known kidney disease were enrolled: 1316 patients with hypertension without diabetes, 208 patients with type 2 diabetes and 93 subjects older than 60 years without hypertension or diabetes. The survey consisted of an interview, consisted of an interview, estimation of glomerular filtration rate (eGFR-MDRD), single urine dipstick detection of proteinuria, hematuria, glucosuria, microalbuminuria. Results: Microalbu minuria with or without proteinuria in combination with eGFR>60 ml/min/1.73m2 was detected in 17% , 41% and 24% of patients with hypertension, diabetes and those above 60 years, respectively. Reduced eGFR (<60 ml/min/1.73m2 ) was found in 23%, 12% and 22% of the same patient groups. The prevalence of CKD markers increased with increasing number of risk factors. Conclusion: High prevalence of CKD markers in at risk population detected by primary care physicians in this collaborative study seems to be the best way to encourage primary care physicians to carry out regular CKD screening (AU)

Antecedentes: El estudio de Belgrado se realizó para detectar personas con marcadores de ERC en poblaciones de riesgo y formar a los especialistas de atención primaria sobre cómo realizar proyecciones de ERC. Métodos: El estudio fue realizado por especialistas de atención primaria de trece centros de salud en colaboración con nefrólogos de centros clínicos. Se incluyó a personas sin enfermedad renal previa conocida: 1316 pacientes con hipertensión sin diabetes, 208 pacientes con diabetes tipo 2 y 93 pacientes de más de 60 años sin hipertensión ni diabetes. El estudio consistía en una entrevista, determinación de la tasa de filtración glomerular estimada (TFGe-MDRD) y detección de proteinuria, hematuria, glucosuria y microalbuminuria con una única tira reactiva de orina. Resultados: Se detectó microalbuminuria con o sin proteinuria en combinación con una TFGe >60 ml/min/1,73m2 en el 17%, el 41% y el 24% de los pacientes con hipertensión, diabetes y mayores de 60 años, respectivamente. Se encontró una TFGe reducida (<60 ml/min/1,73m2 ) en el 23%, el 12% y el 22% de estos mismos grupos de pacientes. La prevalencia de los marcadores de ERC aumentaba cuanto mayor era el número de factores de riesgo. Conclusión: La elevada prevalencia de marcadores de ERC en una población de riesgo detectada por los médicos de atención primaria en este estudio de colaboración parece ser la mejor forma de motivar a estos especialistas para que realicen cribados de ERC con regularidad (AU)

Balkan endemic nephropathy is still present in the Kolubara region, Serbia.

BACKGROUND: Almost 50 years ago Balkan Endemic Nephropathy (BEN) was first described in Serbia in the village of Sopic where the first field examination was carried out in 1971. Our aim was to find out whether BEN is still present in this region. METHODS: Prevalence data on BEN from a field examination run in 1971 were compared with the results of a cross-sectional study conducted in the same village in 1992. In addition, every new case of the disease diagnosed between 1971 and 1992 was recorded retrospectively. The prospective study included 50 members of five BEN families randomly selected from 28 BEN families registered in the village Sopic in 1992. The objective survey and examination of global and tubular kidney function was carried out in all examined persons once yearly in 1998, 1999, and 2000. RESULTS: The overall prevalence of BEN was 6.4% in 1971 and 8.9% in 1992. In the period of 21 years, 161 new BEN patients were detected in 28 families in which the disease had already been recorded. No new family affected by BEN and none of the new patients in 47 families registered previously as nonaffected were discovered. In the prospective study of five BEN families, three new BEN cases were discovered among 50 members, and two patients fulfilled criteria for BEN-suspected ones. CONCLUSION: Balkan Endemic Nephropathy (BEN) is still present in the village of Sopic, but the clinical course of the disease became more protracted over time. New cases of BEN appeared only in the affected families.

Detection of renal dysfunctions in family members of patients with Balkan endemic nephropathy.

BACKGROUND/AIM: Recent studies have questioned whether new cases of Balkan endemic nephropathy (BEN) are occurring. The aim of the present study was to find out whether new members with renal dysfunctions can be identified among family members of BEN patients from the Kolubara region. METHODS: The study included 47 family members of 5 BEN patients on hemodialysis (HD) and 17 members of 3 non-BEN patients on HD. Their medical and epidemiological histories were taken, an objective survey made, and all persons were examined for global and tubular kidney function. RESULTS: Seven BEN family members (2 with previously known BEN) had creatinine clearance (Ccr) below the 75th percentile rank according to sex and age. All non-BEN family members had normal Ccr and no evidence of previous renal disorders. Hypertension was found in 20 (43%) BEN and 6 (35%) non-BEN family members. No significant differences in the frequency of renal function disorders (proteinuria, alpha1-microglobulinuria, urine specific gravity, osmolality, functional excretion of sodium, tubular phosphate resorption) or anemia were found between the groups. Renal disorders were detected in 18 BEN family members without previously detected disease, 3 of whom fulfilled criteria for a diagnosis of BEN and another 2 for BEN-suspected persons. CONCLUSION: New cases of BEN are still arising among the affected families in the Kolubara region.

[Clinical aspects and renal function in patients with endemic nephropathy]. / Prilog proucavanju klinicke slike i funkicije bubrega bolesnika sa endemskom nefropatijom.

Up to now, detailed investigation of tubular function in patients with endemic nephropathy have been performed in the relatively small number of patients who have already been in chronic renal failure /3, 4, 5, 9, 15/. That is why we started this work with the aim to determine renal function of the patients suffering by endemic nephropathy in different stages of the disease, especially in the early stage of the disease. The study included 119 patients with endemic nephropathy who were grouped according to creatinine clearance values into four groups (Table 1). The first group covered the patients with normal creatinine clearance values, and other three covered the patients who were in the different stages of renal failure. The diagnosis of endemic nephropathy was established according to criteria given by Danilovic /7/ and Velimirovic /8/ after ruling out the known renal diseases. The results of clinical and laboratory examinations were processed by appropriate epidemiological and statistical techniques. The results proved that there was no significant difference between sexes of our patients (p > 0.05). Objective examination reveals characteristic tan, pale yellow with copperish glow on the cheeks, in 15.48% of our patients in the early stage of the disease, which is in accordance with the results of Velimirovic /8/. Among nephropathy patients 13% of them had kidney smaller than normal measured by sonography, and even 51% measured by static scintigraphy, in the early phase of the disease (Table 4, Table 5). The earlier works /11,12/ mainly supported that kidneys get smaller during renal insufficiency, and in the early phase of the disease kidneys have a normal size, whereas the later works indicated that even the patients with normal glomerular filtration have smaller kidneys /13,14,15,16/. The laboratory findings and urine analysis of this disease suggested absences of biochemical indicators of inflammation in endemic nephropathy patients (Table 2, Table 3), which is in accordance with the previous in investigations. We noticed correlation between creatinine clearance values and values of serum beta 2 microglobulin (r = = .56; p = = .0002; Figure 1). It has been documented that with decreased of creatinine clearance values, serum values of beta 2 microglobulin increased, in chronic renal failure /22/. Quantitative measuring of proteinuria shows values less than 1.0 g/l in all examined patients. Proteinuria of tubular type has been described in endemic nephropathy /5,8,13,16/. Beta 2 microglobulinuria have been registered at 10.97% patients with normal creatinine clearance values (Table 7). Increased urinary contraction of beta 2 microglobulin is generally accepted as an important feature of endemic nephropathy /19,20,21/. Glicosuria increased with the progression of the disease. Urine osmolallity of endemic nephropathy patients decreased with the progression of chronic renal failure (Table 6). 65.46% of the investigated patients of the first group, who were in the clinically early phase of the disease, had decreased urine osmolallity (measuring by coefficient of osmolallity U osm/Posm). The tubular reabsorbtion of the phosphate decreased with the progression of chronic renal failure and that correlation was statistically significant (r < 0.69; p < 0.05; Figure 2). Fractional tubular excretion of sodium increased with the progression of endemic nephropathy (Table 7). The obteined results of the function of proximal tubular are comparable with the results of the other authors, but in the smaller number of patients /4,13,15,16/. Our results of functional investigations of kidney et patients with endemic nephropathy suggests primary tubular dysfunction, and reduced kidney size and that was registered in the early phase of the disease.