Background and objectives: Improvements in agricultural practices in Croatia have reduced exposure to aristolochic acid viacontaminated flour and risk for development of endemic (Balkan) nephropathy. Therefore, due to reduced exposure to aristolochic acid, 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. 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. ----- Participants, and methods: In this cross-sectional observational study conducted from 2005 to 2010, overall 2822 inhabitans of the villages were enrolled, and 2161 eligible farmers were divided into groups: indigenous inhabitants from endemic nephropathy and non – endemic nephropathy villages and Bosnian immigrants; α1 microglobuline to creatinine ratio 31.5 mg/g and eGFR < 60 ml/min per 1.73m2 were considered to be abnormal. ----- Results: CKD and proximal tubule damage prevalences were significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.9%; p<0.001; 2.0% versus 6.2%; p=0.007, respectively); 20 years ago, Bosnian immigrants observed less Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and less 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). Currently, 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 (OR, 1.64; 95% CI, 1.05 to 2.58; p=0.03), whereas present exposure was not (OR, 1.50; 95% CI, 0.93 to 2.41; p=0.98). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (OR, 0.41; 95% CI, 0.19 to 0.87; p=0.02). ----- Conclusions: 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
