TY - JOUR
T1 - Balkan Endemic nephropathy and the causative role of aristolochic acid
AU - Jelaković, Bojan
AU - Dika, Živka
AU - Arlt, Volker M
AU - Stiborova, Marie
AU - Pavlović, Nikola M
AU - Nikolić, Jovan
AU - Colet, Jean-Marie
AU - Vanherweghem, Jean-Louis
AU - Nortier, Joëlle L
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - Aristolochia species
KW - Balkan endemic nephropathy
KW - aristolochic acid
KW - aristolochic acid nephropathy
KW - upper tract urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85064729249&partnerID=8YFLogxK
U2 - 10.1016/j.semnephrol.2019.02.007
DO - 10.1016/j.semnephrol.2019.02.007
M3 - Review article
C2 - 31054628
SN - 0270-9295
VL - 39
SP - 284
EP - 296
JO - Seminars in Nephrology
JF - Seminars in Nephrology
IS - 3
ER -