Naslov
Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

Autori
Jelaković, Bojan ; Dika, Živka ; Arlt, Volker M ; Stiborova, Marie ; Pavlović, Nikola ; Nikolić, Jovan ; Colet, Jean-Marie ; Vanherweghem, Jean- Louis ; Nortier, Joelle L

Izvornik
Seminars in nephrology (0270-9295) 39 (2019), 3; 284-296

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
Balkan endemic nephropathy ; aristolochic acid nephropathy ; upper tract urothelial carcinoma ; aristolochic acid ; Aristolochia species

Sažetak
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 homebaked 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA