Balkan endemic nephropathy: more questions than answers.
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Balkan Nephropathy↗
Biomedical subjects
P W Hall
Publications and source records attributed to P W Hall.
Urinary protein excretion in children from families with Balkan nephropathy.
We studied the urinary excretion of total protein and five other proteins in urine samples from a total of 831 children and adolescents. The characteristics of the children were: (1.) they resided in areas where Balkan nephropathy (BEN) is endemic and also had family members suffering from BEN; (2.) they resided in areas where BEN is endemic, but the families had no members suffering from the disease; (3.) they lived in nonendemic settlements; (4.) they lived in the city of Nis. Urinary excretion of total protein (TP), albumin (ALB), alpha 2-macroglobulin (alpha 2m), transferrin (TF), IgG, and beta 2-microglobulin (beta 2m) were measured. This study showed that urinary excretion of beta 2m and albumin in children from endemic settlements and from families affected with Balkan nephropathy were not different from the control rural settlements. However, children residing in the city of Nis had significantly increased urinary beta 2m and albumin excretion, over 1.5 to 2.6 times the excretion in the other three groups, although excretion of either protein remained within accepted normal ranges in all groups. The increased excretion of beta 2m and albumin in children from the city of Nis could probably be related to the different growth conditions and/or the effect of toxic environmental factors. These data could serve as a reference base for future comparative studies of urinary protein excretion in children as well as in BEN populations.
Adolescent↗
Altered urinary beta 2-microglobulin excretion as an index of nephrotoxicity.
The experimental and clinical evidence indicate that beta 2-microglobulin (beta 2m) is actively reabsorbed from the glomerular filtrate by receptors on the brush border located in the proximal third of the proximal tubule. Increased beta 2m excretion in the absence of increased filtered load of beta 2m is indicative of nephrotoxicity. The data presented show that urine beta 2m increases and creatinine concentrations decrease within four hours of administration of diatrizoate megalumine (DMG). In 9 of the 20 patients, the urinary excretion of beta 2m (U beta 2m) increased to clearly abnormal values. In 12 of the 20 patients, the beta 2m excretion expressed as mg per g creatinine (Cr), increased from normal (less than 0.30) to an abnormal beta 2m excretion rate. The increased beta 2m excretion per g Cr occurring immediately after DMG administration lead us to conclude that this effect occurs when the nephrotoxic agent is present in the kidney. Based on these data we believe that the onset of abnormal urinary beta 2m excretion coincides with the presence of the causative agent. This criterion therefore, should prove to be useful in determining the time to conduct studies designed to search for the causative agent(s) in Balkan endemic nephropathy.
Adult↗
Beta 2-microglobulinuria as a predictor of death in a population exposed to Balkan endemic nephropathy.
During the year 1974, urinary beta 2-microglobulin (beta 2mu) was measured at monthly intervals using the first-morning urine sample of randomly selected individuals from the BEN affected village of Petka (416 persons) and from the nearby situated control village of Stubica (216 persons). Initial compliance was complete; over 90% of villagers had at least 10 tests performed. beta 2mu, as assessed by radial immunodiffusion (RID), was repeatedly (at least twice) positive in 12% and 1.4% of the populations of the endemic and control villages, respectively. Over the 15 years of follow-up (1974 to 1988), none from the control village developed BEN, while many medical records of the cohort exposed to BEN contained data suggestive of BEN. Death from/with BEN was used as a measure of outcome. Incidence density of 12 was 3.3 per 1000 person/years of observation (19/5723). A single positive beta 2mu test was a sensitive predictor of BEN death (sensitivity = 89.5%). Selecting two or more positive tests as the cut-off point, the specificity and positive predictive value were considerably increased. Using the sulfosalicylic acid test for detection of significant proteinuria, a similar level of validity indices was reached only by four testings.
Aged↗
Beta 2-microglobulin studies in endemic Balkan nephropathy.
The diagnosis of BEN and its differentiation from other chronic interstitial nephropathies are difficult because of the insidious onset as well as nonspecific morphological changes in the kidney. Early diagnosis of this disease is by clinical and laboratory findings which have not been universally accepted. This study was designed to determine if the frequency of increased urinary beta 2-microglobulin (U beta 2m) in village populations at risk to develop BEN was significantly higher than that seen in a control population. Individuals in the two population samples were classified in one of three categories: healthy, suspect or diseased. There were 23 individuals who met the criteria for the clinical diagnosis of BEN. Twenty (87%) of these had one or more positive tests for increased U beta 2m. The prevalence of kidney disease in the endemic village population sample was 13.4 times that for the control village population sample. The data show that the healthy individuals living in a village where BEN is endemic have 6.4 times greater chance of having tubular proteinuria than those living in a control area. The coincidence of the finding of U beta 2m in the urine of 87% of those sick with BEN and in 37 of the 342 (10.8%) people judged to be free of kidney disease suggests that a positive U beta 2m test is an early indicator of exposure to a nephrotoxic agent.
Adult↗
A fifteen year cohort based evaluation of beta 2-microglobulin as an early sign of Balkan endemic nephropathy.
The occurrence of elevated urinary beta 2-microglobulin (U beta 2m) has been established to be more common in village populations living in areas where BEN is endemic when compared to appropriate control population. In addition, beta 2-microglobulinuria is associated with BEN. It has been demonstrated that there is an increase in the U beta 2m in apparently healthy populations located in high risk areas. It is 15 years since the first systematic investigations of U beta 2m in the villages of Brod Posavina were conducted. The purpose of this study was to determine the value of a positive test for tubular proteinuria as defined by increased U beta 2m, in identifying individuals at risk to develop BEN. In these studies we followed two cohorts for 15 years: one group consisted of individuals who were positive for tubular proteinuria by U beta 2m testing in 1974; the second group was an age and sex matched group from the same village who were never positive after 12 testings in 1974. The results show that a positive test for U beta 2m is associated with 9.9 times greater relative risk of developing BEN when compared to controls that had no positive U beta 2m tests.
Adult↗
Relationship of anemia to Balkan endemic nephropathy.
Anemia has been reported to be an early sign of Balkan endemic nephropathy (BEN) occurring before the serum creatinine is elevated. This study was designed to determine if anemia occurred more frequently in an otherwise 'healthy' population living in an area where BEN is endemic when compared to a control population. Also, we wished to determine if any relationship existed between anemia and beta 2-microglobulinuria (beta 2mu) in these populations. The prevalence of anemia in the control village population was 7%, compared to 21.4% of the at-risk village population. These data suggest that anemia is a part of the pathophysiologic picture of endemic nephropathy, and that anemia can be found in an early, non-azotemic phase of the kidney disease.
Anemia↗
Fetal renal tubular function during late pregnancy and diabetes mellitus.
The effect, if any, of diabetes mellitus on the fetal renal tubule has not been previously studied. The concentration of beta2 microglobulin in amniotic fluid is a marker of fetal renal tubular function and normally decreases with advancing gestation, implying increasing tubular function. This relationship was found to be disrupted in 12 diabetic pregnancies, suggesting that the fetal renal tubular cell may represent an example of altered fetal functional maturation occurring during diabetic pregnancy.
Amniotic Fluid↗
Characterization of human beta2-microglobulin by isoelectric focusing.
b2-Microglobulin (B2M) isolated from the urine of normal subjects and patients with cadaveric renal transplantation, showed 2 homologues by isoelectric focusing, one with a pI 5.3, the other with a pI 5.7. These proteins show identical molecular weights by dextran gel filtration and sodium dodecyl sulfate acrylamide gel electrophoresis. The immunogenic reactivity demonstrates partial identity using antiserum to human B2M from 2 different sources.
Beta-Globulins↗
Relation between endemic (Balkan) nephropathy and urinary-tract tumours.
Serum and urine beta 2-microglobulin concentrations were determined in 38-6% of the 869 inhabitants of a village in which both Balkan endemic nephropathy and papillary tumours of the urinary-tract epithelium are common. Over 23% of the "healthy" population had raised serum and/or urine beta 2-microglobulin. 5 of 6 patients with papillary tumours of the renal pelvis, without evidence of renal parenchymal involvement, and 13-4% of the "healthy" population had raised serum-beta 2-microglobulin. It is suggested that overproduction of beta 2-microglobulin, a light-chain-like immune globulin, by the tumour cells may result in a light-chain-like nephropathy--i.e., endemic Balkan nephropathy.
Adenocarcinoma↗
Renal protein metabolism in obstructive uropathy.
Measurements of serum beta 2 microglobulin and creatinine concentrations were determined in 18 patients with lower urinary tract obstruction. Nine patients were azotemic on admission to the hospital. In 3 of these patients who had normal pre-treatment serum levels of beta 2 microglobulin, the correction of obstruction was followed by return of normal renal function. The remaining 6 patients with elevated serum beta 2 microglobulin concentrations on hospitalization, showed no significant improvement in renal function parameters in the post-obstructive period. These data suggest that determination of serum beta 2 microglobulin concentrations is helpful in predicting the return of renal function in azotemic patients with obstructive uropathy.
Aged↗