The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy

Gökmen, M. Refik; Cosyns, Jean‐Pierre; Arlt, Volker M.; Stiborová, Marie; Phillips, David H.; Schmeiser, Heinz H.; Simmonds, Monique S. J.; Cook, H. Terence; Vanherweghem, Jean‐Louis; Nortier, Joëlle; Lord, Graham M.

doi:10.7326/0003-4819-158-6-201303190-00006

Cited by 155 publications

(154 citation statements)

References 61 publications

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“…Plant drugs derived from Aristolochia spp. remain in use today for the treatments of snake bites, arthritis and gout, and coronary artery diseases (8,9), particularly in Asia and some other areas, with the potential for further exposure (10). Aristolochia herbs create a potential public health problem of considerable magnitude (11).…”

Section: Introductionmentioning

confidence: 99%

Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines

Jin

et al. 2016

Cancer Prevention Research

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Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-kB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI-induced hepatocarcinogenesis. Cancer Prev Res; 9(4); 324-34. Ó2016 AACR.

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Section: Introductionmentioning

confidence: 99%

Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines

Jin

et al. 2016

Cancer Prevention Research

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“…12 Balkan endemic nephropathy and Chinese herb nephropathy are the same disease, and they are specifically related to UTUC. 13 They are characterized by a mutation of the p53 gene as a consequence of exposure to aristolochic acid. A significant use of aristolochic acid from Aristolochia plants has been documented in Taiwan, where the incidence of UTUC is estimated to be approximately 20-25% of all urothelial cancers, the highest worldwide.…”

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confidence: 99%

Epidemiology of urothelial carcinoma

2017

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The epithelium lining is defined as the mucosal surfaces of the renal collecting tubules, calyces and pelvis, as well as the ureter, bladder and urethra. The term "urothelium" is used to refer to these surfaces. Upper tract urothelial carcinoma is a rare subset of urothelial cancers with a poor prognosis. Urinary bladder cancer is the most common malignancy involving the urinary system. Upper tract urothelial carcinoma is more common in men than in women, with a male-to-female ratio of 2:1. The incidence of urinary bladder cancer is also higher in men. Cigarette smoking and occupational exposure are the main upper tract urothelial carcinoma and urinary bladder cancer risk factors, while other factors are more specific to the carcinogenesis of upper tract urothelial carcinoma (i.e. Balkan endemic nephropathy, Chinese herb nephropathy). In Egypt until recent years, urinary bladder cancer was the most frequently diagnosed cancer due to Schistosoma haematobium. Substantial knowledge exists regarding the causes of upper tract urothelial carcinoma and urinary bladder cancer, and epidemiological studies have identified various chemical carcinogens that are believed to be responsible for most cases of urothelial carcinoma. In the era of precision medicine, genetic effects might play a direct role in the initiation and progression of urothelial carcinoma.

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“…Aristolochic acid-induced AKI is characterized by proximal tubular epithelial cell death related to oxidative stress . Experimental studies conducted in rabbits and rats confirmed that aristolochic acid was nephrotoxic and led to the concept of aristolochic acid nephropathies that encompasses CKD in Balkan endemic nephropathy and Chinese herb nephropathy (Gökmen et al, 2013). Animal models confirmed the fibrogenic potential of aristolochic acid in vivo (Cosyns et al, 1994;De Broe, 2012;Debelle et al, 2002) both in chronic use and following AKI.…”

Section: Aristolochic Acid-associated Akimentioning

confidence: 78%