scholarly journals Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

2019 ◽  
Vol 39 (3) ◽  
pp. 284-296 ◽  
Author(s):  
Bojan Jelaković ◽  
Živka Dika ◽  
Volker M. Arlt ◽  
Marie Stiborova ◽  
Nikola M. Pavlović ◽  
...  
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.


2009 ◽  
Vol 60 (4) ◽  
pp. 465-483 ◽  
Author(s):  
Annie Pfohl-Leszkowicz

Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract TumoursThis review addresses the unresolved aetiology of several nephropathies and associated upper tract tumours diagnosed all over the world, but especially in the Balkan regions. Studies conducted over the last 35 years point to mycotoxins, mainly ochratoxin A (OTA) as the main culprit. Recent theories however have implicated aristolochic acids (AA). The aim of this review is to put forward arguments in favour of the mycotoxin theory and to show the incoherence of the AA theory. It discusses the differences between the epidemiology of Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN); OTA and AA carcinogenicity; clinical and pathological effects induced by OTA and AA; sources of OTA contamination (food, air, drinking water); OTA- and AA-DNA adduct formation; the role of genetic polymorphisms; and the risk for young children.


2006 ◽  
Vol 50 (6) ◽  
pp. 519-529 ◽  
Author(s):  
Marcel Castegnaro ◽  
Delphine Canadas ◽  
Terry Vrabcheva ◽  
Theodora Petkova-Bocharova ◽  
Ivan N. Chernozemsky ◽  
...  

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

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.


Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 435
Author(s):  
Biljana Dragicevic ◽  
Sonja Suvakov ◽  
Djurdja Jerotic ◽  
Zorica Reljic ◽  
Ljubica Djukanovic ◽  
...  

Background: Experimental data show that superoxide dismutase 2 (SOD2) is involved in ochratoxin (OTA)-induced nephrotoxicity, whereas clinical data indicate the role of SOD2 rs4880 or glutathione peroxidase 1 (GPX1) rs1050450 polymorphisms in end-stage renal disease and urothelial carcinoma risk, known to be the major complications of Balkan endemic nephropathy (BEN). Therefore, we hypothesized that SOD2 and GPX1 gene polymorphisms would influence the risk of BEN and its associated tumors. Materials and Methods: The study was conducted in 207 BEN patients and 86 controls from endemic areas. Results: Individuals with both copies of variant SOD2 allele, known for lower mitochondrial antioxidant protection, are at a significantly higher BEN risk (OR = 2.6, p = 0.021). No association was observed between GPX1 gene polymorphism and BEN risk. Combining SOD2 and GPX1 genotypes did not alter the risk of BEN development. Regarding the risk of urothelial tumors in BEN patients, none of the polymorphisms studied was significantly associated with the risk of these tumors. Conclusions: Polymorphism in SOD2 rs4880 gene affects the risk of BEN development. Hence, SOD2 genotyping could, together with a panel of other enzymes, be used as a biomarker of susceptibility in BEN areas.


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

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