Jelaković Bojan, Vuković Lela Ivana, Karanović Sandra, Dika Živka, Kos Jelena, Dickman Kathleen, Šekoranja Maja, Poljičanin Tamara, Mišić Maja, Premužić Vedran, Abramović Mirta, Matijević Vesna, Miletić Medved Marica, Cvitković Ante, Edwards Karen, Fuček Mirjana, Leko Ninoslav, Teskera Tomislav, Laganović Mario, Čvorišćec Dubravka, Grollman Arthur P
Departments of Nephrology, Hypertension, Dialysis and Transplantation and.
Departments of Nephrology, Hypertension, Dialysis and Transplantation and
Clin J Am Soc Nephrol. 2015 Feb 6;10(2):215-23. doi: 10.2215/CJN.03190314. Epub 2015 Jan 13.
Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal.
CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02).
Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.
克罗地亚农业实践的改进减少了马兜铃酸污染面粉的摄入以及地方性（巴尔干）肾病的发生。因此，有人推测，15至30年前定居在克罗地亚地方性病区的波斯尼亚移民，由于马兜铃酸暴露减少，患地方性肾病的风险会更低。为验证这一假设，分析了波斯尼亚移民过去和现在的马兜铃酸暴露情况、作为地方性肾病标志的近端肾小管损伤情况以及慢性肾脏病的患病率。
设计、地点、参与者与测量方法：在这项2005年至2010年的横断面观察性研究中，2161名农民被分为几组：来自地方性肾病和非地方性肾病村庄的本地居民以及波斯尼亚移民；α-1微球蛋白与肌酐比值>31.5 mg/g且估算肾小球滤过率<60 ml/min per 1.73 m²被视为异常。
波斯尼亚移民的慢性肾脏病和近端肾小管损伤患病率显著低于地方性肾病村庄的居民（分别为6.9%对16.6%；P<0.001；1.3%对7.3%；P=0.003）；20年前，与来自地方性肾病村庄的克罗地亚农民相比，波斯尼亚移民在耕地上观察到的马兜铃较少（41.9%对67.8%），小麦种子中的马兜铃种子也较少（6.1%对35.6%），且购买面包的食用量多于自制面包（38.5%对14.8%，P<0.001）。与15至30年前相比，克罗地亚农民和波斯尼亚移民在其田地里观察到生长的马兜铃植物明显减少。既往马兜铃酸暴露与近端肾小管损伤相关（比值比，1.64；95%置信区间，1.04至2.58；P=0.02），而当前暴露则无此关联（比值比，1.31；95%置信区间，0.75至2.30；P=0.33）。此外，移民身份是近端肾小管损伤的独立负向预测因素（比值比，0.40；95%置信区间，0.19至0.86；P=0.02）。
居住在地方性病区的波斯尼亚移民和克罗地亚本地人摄入马兜铃酸的量比过去显著减少。预计地方性肾病及其相关尿路上皮癌的患病率会随时间下降。
