Aristolochic acid nephropathy caused by ingestion of herbal medicinal products

Author(s):  
M. Refik Gökmen ◽  
Graham M. Lord

Aristolochic acid nephropathy (AAN) is a rapidly progressive renal disease caused by the ingestion of plant products containing aristolochic acid (AA), first described in connection with the use of Chinese herbal medicines. Although the true worldwide extent of this disease is unknown, it is likely to represent a significant cause of chronic kidney disease (CKD) in many parts of the world. Furthermore, recent data have also demonstrated that AA is also the primary aetiological agent in Balkan endemic nephropathy. AAN is notable in its association with urothelial malignancy, with the mechanisms of carcinogenesis now well characterized. Aside from a possible role for corticosteroid therapy in slowing disease progression in selected patients, no disease-specific treatments have yet been shown to alter the course of this nephropathy. Therefore, prevention of exposure to AA and, in affected patients, effective management of the risk of malignancy are key principles in the approach to this condition. Although preparations containing Aristolochia spp. and herbs that can be confused or substituted for Aristolochia have been banned in many countries, other herbal products containing AA have continued to be available to consumers long after these bans have been instituted, highlighting the ongoing need for awareness of this disease.

Author(s):  
Vedran Premužić ◽  
Vanja Ivković ◽  
Ninoslav Leko ◽  
Želimir Stipančić ◽  
Sandra Karanović ◽  
...  

2016 ◽  
Vol 2 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Peter George Mantle ◽  
Diana Herman ◽  
Calin Tatu

In recent years, aristolochic acid has been promoted vigorously as the causal agent of the Balkan endemic nephropathy because of similarities to some other nephropathies, association with DNA adducts and a perception of human exposure via bread. Critical evaluation of the literature exposes flaws in these aspects, and there has been consistent failure of experimental toxicology to mimic either the slow silent bilateral atrophy of the Balkan disease or the transitional cell carcinomas in the upper urothelium. It seems yet premature to promote the curious Balkan disease as aristolochic acid nephropathy without the epidemiological rigour necessary in biomedical research.


2009 ◽  
Vol 9 ◽  
pp. 1360-1373 ◽  
Author(s):  
Ljubinka Jankovic Velickovic ◽  
Takanori Hattori ◽  
Vladisav Stefanovic

The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p< 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p< 0.05), as well as the alteration of p53 (p< 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p< 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p< 0.001). P53 correlated with the grade, growth, and group (p< 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC.


2002 ◽  
Vol 101 (5) ◽  
pp. 500-502 ◽  
Author(s):  
Volker M. Arlt ◽  
Dusan Ferluga ◽  
Marie Stiborova ◽  
Annie Pfohl-Leszkowicz ◽  
Mato Vukelic ◽  
...  

2021 ◽  
Author(s):  
Wenjuan Jiang ◽  
Jiahui Dong ◽  
Changlin Du ◽  
Chuanting Xu ◽  
Songbing Xu ◽  
...  

Abstract Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some herbal medicines, but treatment remains ineffective. We previously found NADPH oxidases 4 (NOX4), which regulates oxidative stress, play an important role in kidney injury model. However, its regulatory mechanism of action in AAN is still obscure. In this study, we established AAN model in vivo, a co-culture system of macrophage and TEC, and macrophage/TEC conditioned media culture model in vitro respectively. We found macrophages infiltration promoted injury,oxidative stress and apoptosis of TEC. Furthermore, the role of macrophage in AAN was dependent on macrophages-derived EV. Importantly, we found that macrophages-derived, Leucine-rich α-2-glycoprotein 1(LRG1)-enriched EV induced TEC injury and apoptosis of via a TGFβR1-dependent process. Mechanistically, macrophages-derived, LRG1-enriched EV mediating TECs injury by upregulating NOX4 in AAN model. This study may help design a better therapeutic strategy to treat AAN patients.


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