Aristolochic acid and the etiology of endemic (Balkan) nephropathy

Grollman, Arthur P.; Shibutani, Shinya; Moriya, Masaaki; Miller, Frederick J.; Wu, Lin; Moll, Ute M.; Suzuki, N.; Fernandes, Andrea; Rosenquist, Thomas A.; Medverec, Zvonimir; Jakovina, Krunoslav; Brdar, Branko; Slade, Neda; Turesky, Robert J.; Goodenough, Angela K.; Rieger, Robert; Vukelić, Mato; Jelaković, Bojan

doi:10.1073/pnas.0701248104

Cited by 528 publications

(639 citation statements)

References 35 publications

(56 reference statements)

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“…This group published a series of papers showing that aristolochic acid is the main risk factor and causative agent of BEN. 17,18 In the last few decades, exposure to this environmental nephrotoxin has decreased due to significant improvements in farming and milling practices. However, further studies are needed to explain why, in a region with a uniform way of farming, the prevalence of BEN remains stable in one village, and while in another it decreases, as presented here.…”

Section: Discussionmentioning

confidence: 99%

Trends in Incidence and Prevalence of Balkan Endemic Nephropathy in the Three Most Affected Villages in Serbia Over a 36-Year Period

Janković

Bukvić²,

Marinković

et al. 2013

Renal Failure

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The study was undertaken with the aim to evaluate trends in incidence and prevalence of Balkan endemic nephropathy (BEN) in the villages Šopić, Petka, and Vreoci, Lazarevac municipality, Serbia. Data concerning BEN notifications in the population-based registry of the Special Hospital for Endemic Nephropathy, Lazarevac were used to evaluate BEN incidence rates in the three villages over the period 1973À2008. Population estimates were based on national census data. All age-adjusted incidence rates were standardized to the European standard population and trends were assessed by Poisson regression model and joinpoint analysis. The prevalence of BEN was obtained in cross-sectional studies carried out in the villages Šopić (1971 and 1992), Vreoci (1971and 2002), and Petka (1971 and 2008. The overall agestandardized incidence rates of BEN in the three villages changed over time. The significant 8.6% annual decrease in the first 16 years of the observed period was followed by a slight increase of 4.6% annually in the last two decades. The agestandardized incidence rates changed over time, being the greatest in the years when the field investigations were made. There was an insignificant change in BEN prevalence in Šopić and Vreoci and a significant decrease in prevalence in Petka. During a 36-year period, 367 new cases of BEN were registered in the three endemic villages and the overall agestandardized incidence rate varied over time. As BEN is a slow-progressing and asymptomatic chronic kidney disease, early detection of BEN can only be achieved by field examination.

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Section: Discussionmentioning

confidence: 99%

Trends in Incidence and Prevalence of Balkan Endemic Nephropathy in the Three Most Affected Villages in Serbia Over a 36-Year Period

Janković

Bukvić²,

Marinković

et al. 2013

Renal Failure

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“…with upper urothelial cancer exclusively affecting farming villagers [1,2,3]. Based on our results, EN is considered to be an environmental form of aristolochic acid nephropathy (AAN) [1,2.3].…”

Section: Endemic (Balkan) Nephropathy (En) Is a Chronic Tubulointerstmentioning

confidence: 99%

“…Gluhovschi et al reported that although therapeutic remedies based on AA products are used in the EN affected area, no relationship between these remedies and the development of EN or of tumors was observed [8]. However, they used HPLC for detection of AA in plasma, which is less sensitive than the mass spectrometry we recently used [1,2]. In addition, when re-analyzing their data, it does appear that AA was used more frequently in the endemic area.…”

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confidence: 95%

Is herbal tea consumption a factor in endemic nephropathy?

et al. 2014

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Endemic (Balkan) nephropathy (EN) is a chronic tubulointerstitial nephropathy frequently associated with upper urothelial cancer exclusively affecting farming villagers [1,2,3]. Based on our results, EN is considered to be an environmental form of aristolochic acid nephropathy (AAN) [1,2.3]. AAN was first reported in 1993 in Belgium and subsequently more AAN cases were reported worldwide as AA has been an integral part of traditional herbal medicines [4]. The extent of this problem was recently documented in Taiwan where precise data on prescriptions of herbal products containing AA is available [5]. Aristolochia spp. has been used for more than 2000 years in the practice of traditional medicine and European physicians were familiar with the use of this plant as well. After its intrinsic toxicity became known, importing Aristolochia herbs was banned in many countries, including Croatia. Nevertheless, products containing AA remain a part of traditional medicine and are sold in many countries that do not have strict control protocols. Recently we reported that AA DNA adducts were present in 95% of patients with EN who underwent surgery for upper urothelial cancers [2] and affirmed the idea that bread contaminated with AA might be the cause of EN [6,7]. However, the causative relationship between AA and EN again raised the question whether bread intake is the only route of ingestion or whether AA was ingested also in EN as a part of folkloric medicine. Gluhovschi et al. reported that although therapeutic remedies based on AA products are used in the EN affected area, no relationship between these remedies and the development of EN or of tumors was observed [8]. However, they used HPLC for detection of AA in plasma, which is less sensitive than the mass spectrometry we recently used [1,2]. In addition, when re-analyzing their data, it does appear that AA was used more frequently in the endemic area. In our opinion, this leaves the question whether herbal tea may play a role in EN still unanswered. In our preliminary study we failed to find any evidence in the group of 1041 Croatian farmers that herbal tea or traditional medicine use is related to EN [9]. The observed differences between Romania and Croatia might reflect cultural and historical differences in traditional medicine. Aiming to resolve this disagreement more conclusively we analyzed whether herbal teas, including those prepared from Aristolochia clematitis, were used more frequently in Croatian and Bosnian residents of an endemic area than in farmers from non-endemic villages. A total of 3168 adults from nine endemic and three non-endemic villages were enrolled (the participation rate was 76.73%). The epidemiological survey was designed to collect demographic, medical, and family history information, as well as dietary and environmental exposures, with an emphasis on the exposure to AA through drinking teas prepared from A. clematitis. Farmers were asked questions: 1): Did you ever use any herbal teas when you were sick?; 2): Did you ever buy, prepare or...

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“…Alternative approaches such as high resolution melting still require a conventional sequencing step and also lack sensitivity. Although the microarray based p53 Amplichip (Roche), improves on sensitivity with a detection limit as low as 2% 31 , it is limited in the type of mutation that it can detect.…”

Section: Introductionmentioning

confidence: 99%

An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukaemia cases using multiple polymerases

et al. 2016

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An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukemia cases using multiple polymerases. Oncogene, 35 (40). pp. [5328][5329][5330][5331][5332][5333][5334][5335][5336] https://doi.org/10. 1038/onc.2016.73 eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. WORRILLOW et al DEEP SEQUENCING OF MUTANT TP53 IN CLL AbstractChronic lymphocytic leukemia (CLL) is the most common clonal B-cell disorder characterised by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current frontline regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway.Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases.

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Aristolochic acid and the etiology of endemic (Balkan) nephropathy

Abstract: Endemic (Balkan) nephropathy (EN),environmental mutagen ͉ p53 mutation ͉ urothelial cancer ͉ DNA adduct

Cited by 528 publications

References 35 publications

Trends in Incidence and Prevalence of Balkan Endemic Nephropathy in the Three Most Affected Villages in Serbia Over a 36-Year Period

Trends in Incidence and Prevalence of Balkan Endemic Nephropathy in the Three Most Affected Villages in Serbia Over a 36-Year Period

Is herbal tea consumption a factor in endemic nephropathy?

An ultra-deep sequencing strategy to detect sub-clonal TP53 mutations in presentation chronic lymphocytic leukaemia cases using multiple polymerases

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