Evaluation of Criteria for the Diagnosis of Balkan Endemic Nephropathy

Abstract

Background. The diagnosis of Balkan endemic nephropathy (BEN) is often made using Danilovic's criteria. The aim of this study was to determine the prevalence, sensitivity, specificity, and predictive value of Danilovic's criteria and several additional indices. Methods. The study included 19 BEN patients, 23 BEN-suspected patients, 34 patients with other kidney diseases, and 23 healthy controls. The sensitivity and specificity of Danilovic's criteria was calculated, and these criteria, in addition to age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume, were combined in a logistic regression. Results. All examined persons were from a BEN-affected village (criterion 1), and all BEN, BENsuspected patients, and 12/23 healthy controls were from BEN families (criterion 2). None of the remaining Danilovic's criteria was found in the healthy controls. The prevalence of proteinuria, low specific gravity, and anemia (criteria 3-5) differed insignificantly among the patient groups. Azotemia and shrunken kidney (criteria 6 and 7) were significantly more frequent in BEN than in other patients. Only proteinuria showed high sensitivity and specificity in differentiating BEN and BEN-suspected patients from healthy persons, but no criteria differentiated BEN or BEN-suspected from other kidney diseases. Proteinuria is a significant predictor of both BEN and BENsuspected vs. healthy persons, and alpha 1-microglobulinuria is a significant predictor of BEN vs. other kidney diseases. Conclusion. Danilovic's criteria enabled a diagnosis of BEN only in chronic renal failure and differential diagnosis between BEN and healthy persons but not between BEN and other kidney diseases. Out of the examined indices of proximal tubular disorders, only alpha 1-microglobulinuria significantly discriminated BEN from other kidney diseases.

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

“…Interestingly, analyses odds ratios and P values were much more in favor of a-1 than b-2 microglobulin. Other works evaluated diagnostic criteria for the diagnosis of EN and concluded that a-1 microglobulinuria significantly discriminated EN from other kidney diseases (50,51). Finally, in our cohort with .2000 enrolled farmers, we obtained the same results (42).…”

Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse

“…Although we have not found any coding differences or RNA expression differences in the AMBP gene between the C57BL/6J and DBA/2J strains, the AMBP gene is noteworthy because tubular low-molecularweight proteinuria, in particular, urinary A1M, is a hallmark of BEN, an environmental disease resulting from chronic dietary exposure to AA (26). The elevation of urinary A1M has been proposed as a specific biomarker of early stage BEN (17,22,55). Elevated urinary A1M is believed to be symptomatic of proximal tubule dysfunction.…”

Could Disappearance of Endemic (Balkan) Nephropathy Be Expected in Forthcoming Decades?

“…The different criteria used across various countries to establish a diagnosis of EN and to classify the endangered population make an exact comparison of the EN prevalence between different endemic areas difficult to achieve [16,18,20,[23][24][25][26][27][28] . In Croatia, the modified WHO criteria have been used for the last 4 decades.…”