How common is Balkan endemic nephropathy among immigrants in endemic regions?

PURPOSE: In the early 1970s, a number of authors described the development of Balkan endemic nephropathy (BEN) in immigrants in endemic regions. The aim of this study was to examine whether immigrants in endemic regions are suffering from BEN today. METHODS: The study involved 193 residents of two endemic regions divided into three groups: two groups of native residents-(1) members of BEN families, (2) members of non-BEN families, and (3) immigrants, who had moved from non-affected settlements to the endemic regions of Kolubara (38 years ago) or Semberia (20 years ago). All persons were subjected to an interview, objective examination, kidney ultrasound, and laboratory analysis to detect the presence of BEN consensus diagnostic criteria. RESULTS: The number of immigrants with BEN biomarkers outside cutoff values was significantly lower than for BEN family members. Five BEN family members met diagnostic criteria for BEN and four for suspected BEN. Although five non-BEN family members had different combinations of BEN biomarkers, all of them had diseases other than BEN in which these biomarkers also occurred. None of the immigrants met the criteria for BEN. Nevertheless, one descendant of an immigrant, a 78-year-old male, whose mother was from a non-BEN family in the Kolubara district, exhibited all the criteria for BEN: alpha1-microglobulinuria, chronic renal failure, and anemia. CONCLUSION: While 30 years ago, BEN was reported equally among immigrants and natives, currently it is diagnosed in some BEN family members in the eighth decade of life, but extremely rarely in immigrants also in old age.

The A-test: assessment of functional recovery during early rehabilitation of patients in an orthopedic ward--content, criterion and construct validity.

BACKGROUND/AIM: The A-test was designed for assessment of functional recovery during early rehabilitation of patients in an orthopedic ward. This performance-based test consists of 10 items for assessing basic activities by a six level ordinal scale (0-5). Total scores can range from 0 to 50, i.e. from inability to perform any activity despite the help of therapists to complete independence and safety in performing all activities. The aim of this study was to examine the A-test validity. METHODS: This prospective study was conducted in an orthopedic ward and included 120 patients [60 patients with hip osteoarthritis that underwent arthroplasty and 60 surgically treated patients with hip fracture (HF)] during early inpatient rehabilitation (1st-5th day). Validity was examined through 3 aspects: content validity--floor and ceiling effect, range, skewness; criterion validity--concurrent validity [correlation with the University of Iowa Level of Assistance Scale (ILAS) for patients with hip osteoarthritis, and with the Cumulated Ambulation Score (CAS) for patients with HF, Spearman rank correlation] and predictive validity [the New Mobility Score (NMS) 4 weeks after surgery, Mann-Whitney U test]; construct validity--4 hypotheses: 1) on the fifth day of rehabilitation in patients underwent arthroplasty due to hip osteoarthritis, the A-test results will strongly correlate with those of ILAS, while the correlation with the Harris hip score will be less strong; 2) in patients with HF, the A-test results will be significantly better in those with allowed weight bearing as compared to patients whom weight bearing is not allowed while walking; 3) results of the A-test will be significantly better in patients with hip osetoarthritis than in those with HF; 4) the A-test results will be significantly better in patients younger than 65 years than in those aged 65 years and older. RESULTS: The obtained results were: low floor (1%) and ceiling (2%) effect, range 0-50, skewness 0.57, strong correlation with ILAS for the patients with hip osteoarthritis (r = -0.97, p = 0.000) and with CAS for the patients with hip fracture (r = 0.91, p = 0.000). The patients with the A-test score 35 and more on the fifth day of rehabilitation (n = 46, Md = 4) had significantly higher NMS rank 4 weeks after surgery than the patients with the A-test score less than 35 (n = 59, Md = 2), (U = 379, z = -6.47, p = 0.000, r = 0.63). All 4 hypotheses were confirmed. CONCLUSION: The A-test is simple and valid instrument for everyday evaluation of pace and degree of functional recovery during early rehabilitation of patients surgically treated in an orthopedic ward.

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.

[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.