title: Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina 29208, USA. karmaus@sc.edu
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.forename: Plamen
authors.initials: P
authors.lastname: Dimitrov
authors.forename: Valeri
authors.initials: V
authors.lastname: Simeonov
authors.forename: Svetla
authors.initials: S
authors.lastname: Tsolova
authors.forename: Angel
authors.initials: A
authors.lastname: Bonev
authors.forename: Rossitza
authors.initials: R
authors.lastname: Georgieva
mesh_terms: D000328:Adult; D032721:Adult Children; D001151:Arsenic / Q000097:blood / Q000302:isolation & purification* / Q000652:urine; D001449:Balkan Nephropathy / Q000209:etiology*; D015415:Biomarkers; D002104:Cadmium / Q000097:blood / Q000302:isolation & purification* / Q000652:urine; D004781:Environmental Exposure; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007407:Interviews as Topic; D007668:Kidney / Q000000981:diagnostic imaging / Q000502:physiology; D007854:Lead / Q000097:blood / Q000302:isolation & purification* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010808:Physical Examination; D012643:Selenium / Q000097:blood / Q000302:isolation & purification* / Q000652:urine; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D002104:Cadmium; D007854:Lead; D012643:Selenium; D001151:Arsenic