title: Beta2-microglobulin and alpha1-microglobulin as markers of Balkan endemic nephropathy, a worldwide disease.
abstract: BACKGROUND
  Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined.
  
  
  METHODS
  This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families.
  
  
  RESULTS
  In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker.
  
  
  CONCLUSIONS
  All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.
authors.affiliation: Institute of Nephrology, Faculty of Medicine, Niš, Serbia. stefan@ni.ac.rs
authors.forename: Vladisav
authors.initials: V
authors.lastname: Stefanović
authors.forename: Ljubica
authors.initials: L
authors.lastname: Djukanović
authors.forename: Rade
authors.initials: R
authors.lastname: Cukuranović
authors.forename: Danica
authors.initials: D
authors.lastname: Bukvić
authors.forename: Višnja
authors.initials: V
authors.lastname: Ležaić
authors.forename: Ivko
authors.initials: I
authors.lastname: Marić
authors.forename: Sanja Simic
authors.initials: SS
authors.lastname: Ogrizovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Jovanović
authors.forename: Predrag
authors.initials: P
authors.lastname: Vlahovic
authors.forename: Ivana
authors.initials: I
authors.lastname: Pešić
authors.forename: Vidosava
authors.initials: V
authors.lastname: Djordjević
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D000510:Alpha-Globulins / Q000652:urine*; D001449:Balkan Nephropathy / Q000175:diagnosis / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D005921:Glomerulonephritis / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009400:Nephrosclerosis / Q000652:urine; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; C016001:alpha-1-microglobulin; D001613:beta 2-Microglobulin