Hanjangsit Kesinee, Karmaus Wilfried, Dimitrov Plamen, Zhang Hongmei, Burch Jim, Tzolova Svetla, Batuman Vecihi
Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA.
Int J Nephrol Renovasc Dis. 2012;5:61-8. doi: 10.2147/IJNRD.S30615. Epub 2012 Apr 4.
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, β(2)-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.
巴尔干地方性肾病（BEN）是一种影响居住在巴尔干地区人群的慢性肾病。尽管这种疾病具有独特的地理特异性，但其病因仍不明确。即使已确定有BEN的阳性家族史，该疾病在后代中如何发展仍不确定。在本文中，我们研究了有BEN父母病史的个体中与BEN发病相关的临床机制，以确定该疾病的早期检测并制定干预措施。我们进行了一项为期5年的前瞻性研究，在第一年和第三年使用标志物来预测第五年BEN的新病例。BEN的新病例根据三个标准定义：BEN的父母病史、肾脏大小减小和肾功能降低。发病病例分为（1）可能病例、（2）确诊病例和（3）合并标记的总发病率。我们评估了与BEN相关的父母病史，并使用路径分析测试了肾长度、肾皮质宽度、β2-微球蛋白、C反应蛋白和肌酐清除率的潜在干预作用。路径分析的结果表明，BEN的父母病史具有直接和间接影响。直接影响在所有三种父母病史模式（双亲、母亲和父亲；优势比分别为71.5、52.3和50.1）中均显著。母亲患BEN的间接影响通过肾长度和肌酐清除率起作用。双亲患BEN由（1）肾长度和肌酐清除率以及（2）单独的肌酐清除率介导。父亲患BEN有三种间接影响：（1）通过肾长度和肌酐清除率，（2）通过肾皮质宽度和肌酐清除率，以及（3）仅通过肾皮质宽度。总之，BEN的家族史导致肾长度和皮质宽度减小以及肌酐清除率下降，进而预测了BEN的发病。
