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The role of a parental history of Balkan endemic nephropathy in the occurrence of BEN: a prospective study

Authors Hanjangsit, Karmaus W, Dimitrov, Zhang, Burch, Tzolova, Batuman

Received 6 February 2012

Accepted for publication 15 February 2012

Published 4 April 2012 Volume 2012:5 Pages 61—68

DOI https://doi.org/10.2147/IJNRD.S30615

Review by Single-blind

Peer reviewer comments 2


Kesinee Hanjangsit1, Wilfried Karmaus1, Plamen Dimitrov2, Hongmei Zhang1, Jim Burch1, Svetla Tzolova2, Vecihi Batuman3,4

1Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA; 2National Center of Public Health Protection, Sofia, Bulgaria; 3Section of Nephrology-Hypertension, Tulane University Medical Center, New Orleans, LA, USA; 4VA Medical Center, New Orleans, LA, USA

Abstract: Balkan endemic nephropathy (BEN) is a chronic kidney disease that affects persons living in the Balkans. Despite the unique geographical specificity of this disease, its etiology has remained unclear. Even if a positive family history of BEN has been identified, it is still uncertain how the disease develops in offspring. In this paper, we examine clinical mechanisms related to the onset of BEN in individuals who have a parental history of BEN to identify early detection of the disease and formulate interventions. We conducted a 5-year prospective study, using markers in years one and three to predict new cases of BEN in year five. New cases of BEN were defined based on three criteria: parental history of BEN, reduced kidney size, and reduced kidney function. Incident cases were divided into (1) probable, (2) definite, and (3) combined labeled total incidence. We evaluated parental history in relation to BEN and tested the potentially intervening effects of kidney length, kidney cortex width, β2-microglobulin, C-reactive protein, and creatinine clearance, using path analyses. The findings of the path analyses suggested that parental history of BEN had both direct and indirect effects. The direct effect was significant for all three modes of parental history (biparental, maternal, and paternal; odds ratios 71.5, 52.3, and 50.1, respectively). The indirect effects of maternal BEN acted via kidney length and creatinine clearance. Biparental BEN was mediated by (1) kidney length and creatinine clearance, and (2) creatinine clearance alone. Paternal BEN had three indirect effects: (1) through kidney length and creatinine clearance, (2) via kidney cortex width and creatinine clearance, and (3) via kidney cortex width only. In conclusion, a family history of BEN led to reduced
kidney length and cortex width, and a decline in creatinine clearance, which in turn predicted the onset of BEN.

Keywords: Balkan endemic nephropathy, incidence of BEN, parental history of BEN, kidney size, β2-microglobulin, creatinine clearance

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