Chronic dietary exposure to aristolochic acid and kidney function in native farmers from a Croatian endemic area and Bosnian immigrants

• Published in: Clinical journal of the American Society of Nephrology Vol. 10; no. 2; pp. 215 - 223
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 06-02-2015
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Agricultural Workers' Diseases - chemically induced; Agricultural Workers' Diseases - diagnosis; Agricultural Workers' Diseases - ethnology; Agricultural Workers' Diseases - physiopathology; Agricultural Workers' Diseases - prevention & control; Agriculture; Alpha-Globulins - urine; Aristolochic Acids - adverse effects; Balkan Nephropathy - chemically induced; Balkan Nephropathy - diagnosis; Balkan Nephropathy - ethnology; Balkan Nephropathy - physiopathology; Balkan Nephropathy - prevention & control; Biomarkers - blood; Biomarkers - urine; Bosnia and Herzegovina - ethnology; Creatinine - blood; Creatinine - urine; Croatia - epidemiology; Cross-Sectional Studies; Diet - adverse effects; Emigrants and Immigrants; Female; Food Contamination; Glomerular Filtration Rate - drug effects; Humans; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - pathology; Kidney Tubules, Proximal - physiopathology; Logistic Models; Male; Middle Aged; Multivariate Analysis; Occupational Exposure - adverse effects; Occupational Exposure - prevention & control; Odds Ratio; Original; Prevalence; Residence Characteristics; Risk Factors; Time Factors; Young Adult; albuminuria; interstitial fibrosis; proximal tubule; CKD
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/CJN.03190314

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.
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.