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Balkan endemic nephropathy-current status and future perspectives.

Pavlović NM - Clin Kidney J (2013)

Bottom Line: The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years.Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN.Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs).

View Article: PubMed Central - PubMed

Affiliation: Clinic of Nephrology, Clinical Centre , Nis , Serbia.

ABSTRACT
Balkan endemic nephropathy (BEN), originally described in 1956, is a unique familial, chronic renal disease encountered with a high-prevalence rate in Serbia, Bulgaria, Romania, Croatia and Bosnia and Herzegovina. The most prominent features of the disease are its endemic nature, long-incubation period, familial clustering of the disease and an unusually high incidence of associated upper urothelial cancer (UUC). There are no clear-cut data on BEN incidence and prevalence, since the studies carried out in different endemic areas yielded contradictory information. In spite of intermittent variations, the incidence of new cases has remained stable over time. It has been estimated that almost 100 000 people are at risk of BEN, whereas 25 000 have the disease. The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years. There are no pathognomonic diagnostic features of BEN, but the set of epidemiological, clinical and biochemical data along with the pattern of pathologic injury in the absence of any other renal diseases are highly suggestive of this entity. Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN. Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs). In light of these later studies, one can raise the question whether AAs could be responsible for previously and currently widespread unrecognized global renal disease and UUC.

No MeSH data available.


Related in: MedlinePlus

TP53 mutational spectra in urothelial carcinomas. (A) TP53 mutations in DNA obtained from UUC in endemic regions of Bosnia, Croatia and Serbia (62 mutations); (B) TP53 mutations in DNA obtained from UUC in Taiwan (113 mutations); (C) TP53 mutations in urothelial carcinomas of the renal pelvis and ureter, worldwide (73 mutations); (D) TP53 mutations in urothelial carcinomas of the renal pelvis, ureter, bladder and nonspecified urinary organs, worldwide (696 mutations)[61].
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SFT049F4: TP53 mutational spectra in urothelial carcinomas. (A) TP53 mutations in DNA obtained from UUC in endemic regions of Bosnia, Croatia and Serbia (62 mutations); (B) TP53 mutations in DNA obtained from UUC in Taiwan (113 mutations); (C) TP53 mutations in urothelial carcinomas of the renal pelvis and ureter, worldwide (73 mutations); (D) TP53 mutations in urothelial carcinomas of the renal pelvis, ureter, bladder and nonspecified urinary organs, worldwide (696 mutations)[61].

Mentions: The finding by Grollman et al. of AA-derived DNA adducts in renal cortical and urothelial tumour tissue of patients with documented BEN, associated with the dominance of the A:T → T:A transversions in the p53 tumour suppressor gene mutational spectrum, was a breakthrough in the identification of AA as an aetiological agent of the upper tract malignancy observed in BEN [64]. The TP53 mutation spectrum in AA-induced UUC displays an unusual pattern that is readily distinguished from all other spectra that have emerged to date from among the 27 000 tumour mutations in the IARC TP53 database. Unique features of this spectrum, including the predominance of A:T → T:A transversions found also in Taiwanese patients with UUC confirmed the hypothesis that all components of the AA signature TP53 mutational spectrum, established in the context of UUC associated with BEN [49], are similarly found in Taiwanese patients with UUC (Figure 4).Fig. 4.


Balkan endemic nephropathy-current status and future perspectives.

Pavlović NM - Clin Kidney J (2013)

TP53 mutational spectra in urothelial carcinomas. (A) TP53 mutations in DNA obtained from UUC in endemic regions of Bosnia, Croatia and Serbia (62 mutations); (B) TP53 mutations in DNA obtained from UUC in Taiwan (113 mutations); (C) TP53 mutations in urothelial carcinomas of the renal pelvis and ureter, worldwide (73 mutations); (D) TP53 mutations in urothelial carcinomas of the renal pelvis, ureter, bladder and nonspecified urinary organs, worldwide (696 mutations)[61].
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400492&req=5

SFT049F4: TP53 mutational spectra in urothelial carcinomas. (A) TP53 mutations in DNA obtained from UUC in endemic regions of Bosnia, Croatia and Serbia (62 mutations); (B) TP53 mutations in DNA obtained from UUC in Taiwan (113 mutations); (C) TP53 mutations in urothelial carcinomas of the renal pelvis and ureter, worldwide (73 mutations); (D) TP53 mutations in urothelial carcinomas of the renal pelvis, ureter, bladder and nonspecified urinary organs, worldwide (696 mutations)[61].
Mentions: The finding by Grollman et al. of AA-derived DNA adducts in renal cortical and urothelial tumour tissue of patients with documented BEN, associated with the dominance of the A:T → T:A transversions in the p53 tumour suppressor gene mutational spectrum, was a breakthrough in the identification of AA as an aetiological agent of the upper tract malignancy observed in BEN [64]. The TP53 mutation spectrum in AA-induced UUC displays an unusual pattern that is readily distinguished from all other spectra that have emerged to date from among the 27 000 tumour mutations in the IARC TP53 database. Unique features of this spectrum, including the predominance of A:T → T:A transversions found also in Taiwanese patients with UUC confirmed the hypothesis that all components of the AA signature TP53 mutational spectrum, established in the context of UUC associated with BEN [49], are similarly found in Taiwanese patients with UUC (Figure 4).Fig. 4.

Bottom Line: The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years.Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN.Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs).

View Article: PubMed Central - PubMed

Affiliation: Clinic of Nephrology, Clinical Centre , Nis , Serbia.

ABSTRACT
Balkan endemic nephropathy (BEN), originally described in 1956, is a unique familial, chronic renal disease encountered with a high-prevalence rate in Serbia, Bulgaria, Romania, Croatia and Bosnia and Herzegovina. The most prominent features of the disease are its endemic nature, long-incubation period, familial clustering of the disease and an unusually high incidence of associated upper urothelial cancer (UUC). There are no clear-cut data on BEN incidence and prevalence, since the studies carried out in different endemic areas yielded contradictory information. In spite of intermittent variations, the incidence of new cases has remained stable over time. It has been estimated that almost 100 000 people are at risk of BEN, whereas 25 000 have the disease. The clinical signs and symptoms of BEN are non-specific and often remain unrecognized for years. There are no pathognomonic diagnostic features of BEN, but the set of epidemiological, clinical and biochemical data along with the pattern of pathologic injury in the absence of any other renal diseases are highly suggestive of this entity. Although the aetiology has been extensively studied, fostering the publication of various hypotheses, only one of them has provided conclusive evidence related to the aetiology of BEN. Studies conducted over the past decade have provided particularly strong arguments that BEN and UUC are caused by chronic poisoning with aristolochic acids (AAs). In light of these later studies, one can raise the question whether AAs could be responsible for previously and currently widespread unrecognized global renal disease and UUC.

No MeSH data available.


Related in: MedlinePlus