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. Conclusion: 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.

Familial versus environmental factors in Balkan endemic nephropathy in Mehedinti county, Romania, by means of albuminuria and tubular biomarkers: preliminary study

“…19 Comparing BEN patients with healthy controls, Stefanovic et al consider that urinary beta 2-microglobulin has higher sensitivity and specificity than alpha-1-microglobulin. 20 The GFR was lower in neighbors of BEN patients than in both relatives of BEN patients having lived in the area for more than 20 years in the BEN area and in relatives of BEN patients having lived there for less than 20 years. Low GFR could be related to the length of residence in the endemic area.…”

Chronic Dietary Exposure to Aristolochic Acid and Kidney Function in Native Farmers from a Croatian Endemic Area and Bosnian Immigrants

“…Also, we determined a-1CR and urine albumine to urine creatinine ratio in a single spot urine sample. However, recent studies suggest that similar measurements of a-1CR are a reliable marker for EN (23,25,(39)(40)(41)(42)(43)(44)(45) and other chronic tubulointerstitial diseases, such as cadmium nephropathy (46)(47)(48)(49). Most authors believe that a-1 microglobulin has advantages over b-2 microglobulin.…”

Specifičnost i senzitivnost biomarkera balkanske endemske nefropatije

“…To ukazuje da mnoge osobe iz endemskih porodica imaju neotkrivenu BEN, što nameće potrebu da se provjeri pouzdanost biomarkera koji će omogućiti dijagnozu BEN. Zbog toga je provjera specifičnosti pojedinih biomarkera za dijagnozu BEN odabrana za predmet našeg istraživanja, kao i nekoliko istraživanja urađenih tokom protekle decenije [7,8,[12][13][14].…”

“…Iako Stefanović i sar. [13] ukazuju da beta-2 mikroglobulin ima veću senzitivnost i specifičnost od alfa1-mikroglobulina u razlikovanju bolesnika sa BEN od zdravih, oba ova biomarkera su se u tom radu pokazala kao značajni prediktori BEN. Međutim, postoje razlike u graničnoj vrijednosti alfa1-mikroglobulina po kojoj se najtačnije razlikuje BEN od zdravih.…”

“…U našem radu to je vrijednost od 1,08 mg/ mmol kreatinina, Stefanović i sar. [13] navode sličnu vrijednost od 1,12 mg/mmol kreatinina, Đukanović i sar. [7] 1,37 mg/mmol kreatinina, ali Dika [8] navodi vrijednost od 23,5 mg/g kreatinina (2,66 mg/mmol kreatinina) koja se preporučuje i u nedavnoj preporuci za dijagnozu BEN [6].…”