Bojan Jelaković1, Ivana Vuković Lela2, Sandra Karanović1, Živka Dika1, Jelena Kos1, Kathleen Dickman3, Maja Šekoranja4, Tamara Poljičanin5, Maja Mišić6, Vedran Premužić1, Mirta Abramović7, Vesna Matijević8, Marica Miletić Medved9, Ante Cvitković9, Karen Edwards10, Mirjana Fuček11, Ninoslav Leko12, Tomislav Teskera12, Mario Laganović1, Dubravka Čvorišćec11, Arthur P Grollman3. 1. Departments of Nephrology, Hypertension, Dialysis and Transplantation and. 2. Departments of Nephrology, Hypertension, Dialysis and Transplantation and ivemedex@yahoo.com. 3. Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York. 4. Faculty for Natural Sciences, University of Zagreb, Zagreb, Croatia; 5. National Institute for Public Health, Zagreb, Croatia; 6. Cytology Unit, Slavonski Brod, Croatia; 7. Outpatient Clinic Bebrina, Bebrina, Croatia; 8. Outpatient Clinic Slavonski, Kobaš, Croatia; 9. Institute for Public Health County Brodsko-Posavska, Slavonski Brod, Croatia; 10. Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California, Irvine, Irvine, CA; and. 11. Clinical Laboratory Diagnostics, School of Medicine, University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia; 12. General Hospital, "Josip Benčević", Department of Internal Medicine, Dialysis Unit.
Abstract
BACKGROUND AND OBJECTIVES: 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. RESULTS: 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). 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.
BACKGROUND AND OBJECTIVES: 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. RESULTS: 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). 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.
Authors: Tjasa Hranjec; Anamarija Kovac; Jelena Kos; Wenyang Mao; John J Chen; Arthur P Grollman; Bojan Jelaković Journal: Croat Med J Date: 2005-02 Impact factor: 1.351
Authors: M Ikeda; T Ezaki; T Tsukahara; J Moriguchi; K Furuki; Y Fukui; H Ukai; S Okamoto; H Sakurai Journal: Arch Environ Contam Toxicol Date: 2005-01 Impact factor: 2.804