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At least 19 recordsLinked to original sources
PubMed1996

Identification of a novel subset of T lymphocytes in patients with Balkanic nephropathy.

Balkanic Nephropathy (BN) is characterized by: an incidence limited to a geographic area: a familial character and a slow progressive evoluation towards chronic renal failure associated with the symmetrical reduction of the kidney size. The etiology of BN is unknown. The aim of our study was to find out the immune alterations in BN pathology. In the BN patients we identified a novel subset of the CD3+ CD16+ and CD56+ T cells expressing the phenotypic characteristics of both T lymphocytes and NK cells. The analysis of various subpopulations of lymphocytes, however, showed no quantitative differences in comparison with healthy subjects and healthy subjects from the endemic area.

Adult↗
PubMedDate not supplied

CD3+, CD16+, CD56+ cells: a novel subset of T lymphocytes from patients with Balkanic nephropathy.

Balkanic Nephropathy (BN) is characterized by: an incidence limited to a geographic area; a familial character and a slow progressive evolution towards chronic renal failure associated with the symmetrical reduction of the kidney size. The aim of our study was to find out the immune alterations in BN pathology. The analysis of various subpopulations of peripheral lymphocytes obtained from patients with BN showed no quantitative differences in comparison with healthy subjects and healthy subjects from the endemic area. In the BN patients we identified a novel subset of the CD3+, CD16+, CD56+ cells expressing the phenotypic characteristics of both T lymphocytes and NK cells.

Adult↗
PubMedDate not supplied

The level of interleukin-2 and of soluble interleukin-2 receptor in patients with Balkan nephropathy.

Balkan Nephropathy (BN) is defined as a clinical entity with unknown etiology. The involvement of immune system in pathogenesis of BN is not well defined yet. The aim of this study was to gain more insight into the cellular immune mechanisms in BN. We determined some factors implied in cellular immunity, such as the serum level of IL-2 and of IL-2 soluble receptor (sIL-2R), and the presence of IL-2 receptor alpha chain (CD25) on T cells membrane. The study was performed on 15 patients with BN, 15 patients with Chronic Pyelonephritis (CPN), and 10 healthy controls from a non-endemic area. Our study showed no significant differences between IL-2 level and CD25+ cells percentage in CPN compared to controls, but a significantly increased level of sIL-2R. The BN sIL-2R is significantly lower than sIL-2R in CPN, and associates an important T cell activation (high CD25+ presence, elevated IL-2 level) compared to CPN. Our conclusion is that while the high sIL-2R level could down modulate T cell activity in CPN, BN sIL-2R level is ineffective in limiting the activation effects of IL-2 on T cells. The results suggest that cellular immunity could have a role in the pathogenesis of N.

Balkan Nephropathy↗
PubMed1999

Importance of sodium dodecyl sulfate pore-graduated polyacrylamide gel electrophoresis in the differential diagnostic of Balkan nephropathy.

Balkan nephropathy (BN) is an endemic disease, which leads to end-stage renal failure and artificial renal replacement therapy. Pathologically it is characterized by progressive interstitial nephritis in a large population of villages situated in the proximity of a bend of the Danube up to a distance of 100 km from the river in several parts of Bulgaria, Romania, and the former Yugoslavia. The urinary proteins of 19 patients with BN from the region of Vratza, Bulgaria were examined using ultrathin layer sodium dodecyl sulfate (SDS) pore-graduated polyacrylamide gel electrophoresis (PAGE) and silver staining. The documentation of urinary proteins pattern was performed using laser densitometry and consecutive electronic processing for the purpose of characterizing and quantifying protein excretion. Our results show that the proteinuria of BN is predominantly tubular, consisting of low molecular weight species (10-65 kilodaltons). The amount of tubular protein changes with the progression of the disease. SDS-polyacrylamide gel electrophoresis (PAGE) is a diagnostic method for early diagnosis of tubular failure in BN. Using our method of SDS-PAGE, tubular failure can be detected even at a total protein concentration below 0.1 g/L and when the serum creatinine concentration is normal. Additionally, our method of SDS-PAGE supports the differentiation of BN from glomerular disease.

Aged↗
PubMed2002

Increased urinary albumin excretion in children from families with Balkan nephropathy.

Balkan nephropathy (BN) has not been described in children. However, some previous studies have revealed abnormalities of the urinary tract in children from families with BN. In the present study, urinary excretion of albumin was studied in 703 healthy children, age 9-13 years, from endemic and non-endemic settlements around the South Morava River. Since BN is an environmentally induced disease, with possible seasonal variation of toxicant(s), children were studied three times a year: spring, autumn, and winter. After a water load of 15 ml/kg body weight, a 3-h urine sample was collected, from 7 to 10 a.m. Albumin excretion in urine was highest in children from families with BN in all three periods investigated. It was significantly different from excretion in children from the city, and in autumn it was also different ( P<0.01) from children in non-endemic families. Correlation analysis of albumin excretion with some urinary markers of tubular nephrotoxicity shows the highest correlation with both beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase in endemic villages in autumn. If the upper limit of albumin excretion is set at 8.5 mg/mmol creatinine, then in autumn increased albumin excretion was found in 15 of 229 children from endemic settlements and in only 5 of 454 children from non-endemic areas ( P<0.0001). Evidence is presented that in autumn children from families with BN excreted significantly more albumin than those from non-endemic families but living in the same settlements, or from children living outside of the endemic region in the city of Nis.

Acetylglucosaminidase↗
PubMed1991

Possible pathogenetic role of low-molecular-weight proteins in Balkan nephropathy.

Balkan endemic nephropathy (BEN) is a tubulointerstitial disease characterized by increased-low-molecular-weight protein (LMWP), most notably, beta 2-microglobulin (beta 2m) excretion in urine. We previously demonstrated that two species of LMWPs, immunoglobulin light chains (LC) and recombinant alpha interferon (rIF), are toxic at proximal tubule cell membrane level. Myeloma LCs and rIF inhibit Na-dependent uptake of 14C-L-alanine and 14C-D-glucose by rat renal brush border membrane (BBM) vesicles at half-maximal inhibitory concentrations, IC50, ranging from 68 to 140 microM for LCs, and 5.4 to 18 nM for rIF. We further demonstrated that LCs bind to high-capacity, low-affinity sites on BBM with dissociation constants (Kd) ranging from 16 to 118 microM, a range similar to IC50s observed with the same LCs. Binding site occupancy is inversely related to alanine (r = -0.95, P less than 0.01), and glucose uptake (r = -0.96, P less than 0.01), implying that LC nephrotoxicity is determined by its binding to BBM. beta 2m shares behavioral and structural similarities with both LC and rIF. Preliminary studies in our laboratory showed that unlabeled LCs compete for the same binding sites on BBM with beta 2m. These observations confirm that all LMWP, including beta 2m, are potentially nephrotoxic. Thus, the characteristic beta 2-microglobulinuria of BEN may be more than a consequence of tubular dysfunction, and may play a pathogenetic role.

Animals↗
PubMedDate not supplied

Studies on the familial character of endemic Balkan nephropathy. Possible role of the toxic hydric factor in the determination of "familial agglomerations" in endemic Balkan nephropathy.

The study was carried out in an attempt to explain the familial character of endemic Balkan nephropathy and of agglomeration of cases in certain households and in the ascendency of certain families. The hypotheses of a genetic disease or that of an infectious etiology have been taken into consideration in previous studies - by chromosomal analyses and statistical-mathematic tests of contagiousness - without being able to find arguments in support of one or the other hypotheses. This study brings important elements in favour of the possible role of ecologic factors and mainly of the hydrictoxic one, in the determination of the familial agglomerations in endemic nephropathy. Thus using radionuclear determination methods, we could demonstrate in a locality of the endemic area that around the water sources with high content of nephrotoxic oligoelements (cadmium, chromium, manganese, cobalt) there are more diseased families than around water sources poorer in these oligoelements.

Balkan Nephropathy↗
PubMed1999

Isolation of a coronavirus from kidney biopsies of endemic Balkan nephropathy patients.

Endemic Balkan nephropathy (EBN) is a kidney disease of unknown etiology limited to Bulgaria, Rumania and former Yugoslavia. Primary kidney tissue cultures were established as explants from tissue obtained at operations from 5 EBN patients with urinary tract tumors. Four out of the five biopsy specimens on extended culture incubation at 33 degrees C yielded a coronavirus virus (EBNV) which was cytopathogenic for human fibroblast and Vero cells. In cells inoculated with EBNV, cytoplasmic immunofluorescence was found using antisera for human coronaviruses OC43 and 229E as well as the porcine transmissible gastroenteric virus and avian (chicken) bronchitis virus. In neutralization tests, EBNV failed to react with antisera to these viruses. Using hyperimmune serum raised with EBNV, positive cytoplasmic immunofluorescence was seen with cells infected with OC43, 229E, TGV and significantly with the kidney tissue of the biopsy specimens from the EBN patients. A screen for neutralizing antibody using the EBN virus revealed that 87.2% of EBN patients on dialysis were positive, also 74% of people from an endemic area were also positive, while only 13.5% from outside were positive. It is suggested that a coronavirus is involved in the etiology of the disease and that humans are an incidental host of a coronavirus zoonosis.

Animals↗
PubMed1991

Beta 2-microglobulin in patients with Balkan nephropathy and in healthy members of their families.

The aim of this study was to investigate serum levels, urinary excretion and in vitro peripheral blood mononuclear cell (PBMC) production of beta 2-microglobulin in patients with Balkan nephropathy and their families. Increased urinary beta 2-microglobulin excretion was found in Balkan nephropathy, chronic pyelonephritis and glomerulonephritis patients, being highest in the first group. The serum level of beta 2-microglobulin in Balkan nephropathy patients correlated with residual kidney function. Synthesis of beta 2-microglobulin by PBMC, untreated or stimulated by PHA, was not increased in Balkan nephropathy patients or their healthy family members compared to the control group of healthy persons living outside of an endemic region. This study has shown that the increased serum beta 2-microglobulin level in Balkan nephropathy patients is the consequence of the glomerular filtration rate (GFR) reduction. Urinary beta 2-microglobulin excretion was found increased not only in patients but in some healthy members of nephropathic families. beta 2-microglobulin therefore can serve as a marker of the early tubular damage in Balkan nephropathy. However, urinary beta 2-microglobulin is not specific for Balkan nephropathy, lacking specificity required for screening purposes. The different patterns of serum and urinary beta 2-microglobulin, and other urinary proteins, in patients with Balkan nephropathy from patients with chronic pyelonephritis and glomerulonephritis favor the opinion that Balkan nephropathy is a separate clinical entity.

Albuminuria↗
PubMed1987

Epidemiological evidence on Balkan nephropathy as a viral disease.

Balkan nephropathy is a chronic kidney disease of a completely unknown etiology. Most epidemiologists believe that the disease has been caused by viruses, though all attempts to prove such a relationship have been fruitless. A common feature of most of the clues offered for elucidating the role of the viruses, is that they interfere with the epidemiological evidence on BN. Therefore, a hypothesis is put forward that the disease has been caused by slow viruses transmitted by rodents which contaminate food and articles in the house. Such an explanation fits most of the existing epidemiological data.

Animals↗
PubMed1985

[Balkan nephropathy and transitional cell carcinoma. Pathogenetic problems and the early phase of cancerogenesis].

Balkan Nephropathy belongs to the group of primary chronic interstitial nephropathy with tubular functional abnormalities at early clinical stage. This disease may occur at any age and may affect all members of the same family including the children existing in them in latent form. The coincidental occurrence of Balkan Nephropathy and urothelial carcinoma has been very often observed. The actual problems of early Balkan Nephropathy pathogenesis and carcinogenesis are considered.

Adult↗
PubMed1991

Urinary tract tumors and Balkan nephropathy in the South Morava River basin.

The aim of this investigation was to study the frequency of urinary tract tumors (UTT) in settlements around the South Morava River and its tributaries where Balkan nephropathy is endemic. For this purpose 659 surgery and autopsy records of patients with UTT were reviewed. The records came from 25 counties and 1279 settlements classified as endemic, hypoendemic and nonendemic. Upper tract urothelial, urinary bladder and kidney tumors were included in the evaluation. A highly significant geographic correlation between Balkan nephropathy and UTT localized in renal pelvis and ureter was noted in the South Morava River valley. These tumors were 57 and 61.8 times more frequent in endemic settlements than in control rural and city populations free of Balkan nephropathy. The frequency of urinary bladder tumors in endemic settlements was also increased compared with the nonendemic villages and large cities, up to 11.9 and 8.5 times, respectively. In endemic settlements, upper urinary tract tumors were five times and tumors of urinary bladder were seven times more frequent in families with Balkan nephropathy than in those without, and up to 224 times more frequent than in the city families. Familial clustering of UTT was also noted. The geographic correlation between Balkan nephropathy and UTT supports the speculation that these disorders share a common etiology.

Aged↗
PubMed1989

Aetiology of Balkan nephropathy: a reappraisal after 30 years.

Balkan nephropathy (BN) has been a complete aetiological puzzle for many years. Intense research produced many controversial results, but also helped some clues to be traced. Thus, it became rather obvious that the disease is caused by environmental factors (though it may be, to some extent, genetically controlled). Among live agents, slow viruses are the only (and theoretically very attractive) possible cause of both BN and urothelial tumours, which occur frequently in BN endemic areas. Apart from occasional visualization of virus-like particles, other evidence supporting this hypothesis has been lacking. The role biological products, particularly fungal toxins, needs to be further defined. An excess of any heavy metal or radioactive substance as a cause of BN is very unlikely indeed; however, a deficiency of a bio-essential element could not be ruled out. Many epidemiological data indicate that water might be a transmitter of the agent(s). A wide range of ions and minerals have been incriminated, but up to now most of the studies have provided negative or inconclusive results. Organic compounds in well water have never been sufficiently considered. Another ignored area are unstable and, particularly, photosensitive substances. Fertilizers, pesticides, analgesics, local herbs and teas have no causal relation to BN.

Balkan Nephropathy↗
PubMed1980

[Endemic Balkan nephropathy (author's transl)].

Endemic Balkan nephropathy (EBN) is a chronic interstitial nephritis which may occur at any age and may affect several members of the same family. The condition is slowly progressive and can more easily be diagnosed in its advanced than in its early stages. Early symptoms include severe anaemia and increased plasma aminoacids, alkaline phosphatases and gamma 2 and alpha globulins. Eosinophilia is not uncommon. Loss of urine concentration power and high beta 2 microglobin urinary levels are among the earliest signs of EBN and of considerable diagnostic value. Renal biopsy shows invasive sclerosis, IgG and IgA deposits in glomerular vessels and Bowman's capsule walls and, characteristically, osmiophilic granulations within the mitochondria of proximal tubule cells; the mitochondria may in due course burst and disappear. Atrophic or dystrophic changes may develop in the stomach, upper intestine and liver. The aetiology of EBN remains undetermined, but chronic intoxication with drinking water polluted by silicates released during soil erosion seems to be the most probable cause. Silicates may act directly or by inducing an immune process.

Adolescent↗