Balkan endemic nephropathy is a chronic tubulointerstitial disease with insidious onset, slowly progressing to end-stage renal disease and frequently associated with urothelial carcinoma of the upper urinary tract (UTUC). It was described in South-East Europe at the Balkan peninsula in rural areas around tributaries of the Danube River. After decades of intensive investigation, the causative factor was identified as the environmental phytotoxin aristolochic acid (AA) contained in Aristolochia clematitis, a common plant growing in wheat fields that was ingested through home-baked bread. AA initially was involved in the outbreak of cases of rapidly progressive renal fibrosis reported in Belgium after intake of root extracts of Aristolochia fangchi imported from China. A high prevalence of UTUC was found in these patients. The common molecular link between Balkan and Belgian nephropathy cases was the detection of aristolactam-DNA adducts in renal tissue and UTUC. These adducts are not only biomarkers of prior exposure to AA, but they also trigger urothelial malignancy by inducing specific mutations (A:T to T:A transversion) in critical genes of carcinogenesis, including the tumor-suppressor TP53. Such mutational signatures are found in other cases worldwide, particularly in Taiwan, highlighting the general public health issue of AA exposure by traditional phytotherapies.

Clinical Centre Serbia Belgrade Serbia

Department of Analytical Environmental and Forensic Sciences Medical Research Council Public Health England Centre for Environment and Health King's College London London United Kingdom; National Institute for Health Research Unit Health Impact of Environmental Hazards King's College London in partnership with Public Health England and Imperial College London London United Kingdom

Department of Biochemistry Faculty of Science Charles University Prague 2 Czech Republic

Department of Human Biology and Toxicology Faculty of Medicine and Pharmacy University of Mons Mons Belgium

Nephrology Department Erasme Hospital Université Libre de Bruxelles Brussels Belgium

Nephrology Department Erasme Hospital Université Libre de Bruxelles Brussels Belgium; Laboratory of Experimental Nephrology Faculty of Medicine Université Libre de Bruxelles Brussels Belgium

School of Medicine University of Zagreb Department of Nephrology Hypertension Dialysis and Transplantation University Hospital Centre Zagreb Zagreb Croatia

Serbian Medical Society Branch Niš Niš Serbia

Citace poskytuje Crossref.org

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