Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study.

BACKGROUND: The etiology of Balkan Endemic Nephropathy, (BEN), a tubulointerstitial kidney disease, is unknown. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, similar manifestations are reported to occur in other regions, for instance Tunisia and Sri Lanka. A number of explanations have been stated including lignites, aristolochic acid, ochratoxin A, metals, and metalloids. Etiologic claims are often based on one or a few studies without sound scientific evidence. In this systematic study, we tested whether exposures to metals (cadmium and lead) and metalloids (arsenic and selenium) are related to Balkan Endemic Nephropathy. METHODS: In 2003/04 we recruited 102 adults whose parents had BEN and who resided in one of three communities (Vratza, Bistretz, or Beli Izvor, Bulgaria). A control group comprised of 99 adults having non-BEN hospitalized parents was enrolled in the study during the same time. We conducted face-to-face interviews, ultrasound kidney measurements, and determined kidney function in two consecutive investigations (2003/04 and 2004/05). Metals and metalloids were measured in urine and blood samples. To assess the agreement between these consecutive measurements, we calculated intraclass correlation coefficients. Repeated measurement data were analyzed using mixed models. RESULTS: We found that cadmium and arsenic were associated with neither kidney size nor function. Lead had a significant but negligible effect on creatinine clearance. Selenium showed a weak but significant negative association with two of the four kidney parameters, namely creatinine clearance and beta2-microglobulin. It was positively related to kidney length. These associations were not restricted to the offspring of BEN patients. Adding credence to these findings are reports showing comparable kidney effects in animals exposed to selenium. CONCLUSION: The findings of this 2-year follow-up study indicate that metals and metalloids do not play a role in the etiology of Balkan Endemic Nephropathy. Against the assumption in the literature, selenium was not protective but a risk factor. Since comparable associations were observed in animals, future studies are needed to explore whether selenium may have adverse renal effects in humans.

Increased blood pressure in adult offspring of families with Balkan endemic nephropathy: a prospective study.

BACKGROUND: Previous studies have linked smaller kidney dimensions to increased blood pressure. However, patients with Balkan Endemic Nephropathy (BEN), whose kidneys shrink during the course of the disease, do not manifest increased blood pressure. The authors evaluated the relationship between kidney cortex width, kidney length, and blood pressure in the offspring of BEN patients and controls. METHODS: 102 offspring of BEN patients and 99 control offspring of non-BEN hospital patients in the Vratza District, Bulgaria, were enrolled in a prospective study and examined twice (2003/04 and 2004/05). Kidney dimensions were determined using ultrasound, blood pressure was measured, and medical information was collected. The parental disease of BEN was categorized into three groups: mother, father, or both parents. Repeated measurements were analyzed with mixed regression models. RESULTS: In all participants, a decrease in minimal kidney cortex width of 1 mm was related to an increase in systolic blood pressure of 1.4 mm Hg (p = 0.005). There was no association between kidney length and blood pressure. A maternal history of BEN was associated with an increase in systolic blood pressure of 6.7 mm Hg (p = 0.03); paternal BEN, +3.2 mm Hg (p = 0.35); or both parents affected, +9.9 mm Hg (p = 0.002). There was a similar relation of kidney cortex width and parental history of BEN with pulse pressure; however, no association with diastolic blood pressure was found. CONCLUSION: In BEN and control offspring, a smaller kidney cortex width predisposed to higher blood pressure. Unexpectedly, a maternal history of BEN was associated with average increased systolic blood pressure in offspring.

Cytogenetic effects of hexavalent chromium in Bulgarian chromium platers.

The aim of the present study was to evaluate the genotoxic effects of hexavalent chromium (Cr(VI)) in vivo in exposed Bulgarian chromium platers by using classical cytogenetic and molecular cytogenetic analyses of peripheral lymphocytes and exfoliated buccal cells. No significant difference was observed between the exposed workers and the controls with regard to the frequency of cells with chromosome aberrations (CAs) using conventional Giemsa staining and in the frequency of sister chromatid exchanges (SCEs). However, there was a significant increase in the number of cells with micronuclei (MN) in peripheral lymphocytes from chromium exposed workers as compared to the controls. In the buccal cells from these workers, this increase was even more pronounced. Cytosine arabinoside (AraC), an inhibitor of DNA synthesis and repair, was found to significantly increase the levels of MN in vitro in the lymphocytes of both groups. The increase was more expressed in the lymphocytes of chromium exposed workers. Both centromere positive (C(+)) as well as centromere negative (C(-)) MN were observed by the fluorescence in situ hybridization (FISH) technique in both of the cell types studied. No difference between C(+) and C(-) MN frequencies was found in the lymphocytes as well as in the buccal cells. Thus, Cr(VI) appears to have both clastogenic as well as aneugenic effects in humans.