Reduced Kidney Size in Adult Offspring of Balkan Endemic Nephropathy Patients and Controls: A Prospective Study

Hanjangsit, Kesinee; Karmaus, Wilfried; Dimitrov, Plamen; Tsolova, Svetla; Batuman, Vecihi; Simeonov, Valeri; Bonev, Angel

doi:10.1097/maj.0b013e3181e2353e

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Balkan endemic nephropathy (BEN) is a chronic renal fibrotic disease affecting residents of multiple Balkan countries alongside the Danube River, including Bosnia-Herzegovina, Bulgaria, Croatia, Macedonia, Serbia, and Romania. − Key epidemiologic features of the disease include its endemic nature, occurrence only in adults, familial incidence but without inheritance, and close association with the development of carcinomas of the upper urinary tract. ,,− Over 25,000 individuals are estimated to be suffering from BEN and 100,000 are at risk of developing the disease. ,,− …”

Section: Introductionmentioning

confidence: 99%

Effects of Diet on Aristolochic Acid-DNA Adduct Formation: Implications for Balkan Endemic Nephropathy Etiology

Zhang

Chan

Pavlović

et al. 2023

Chem. Res. Toxicol.

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Prolonged exposure to aristolochic acids (AAs) through AA-containing herbal medicine or AA-contaminated food is associated with the development of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), both public health risks to which the World Health Organization is calling for global action to remove exposure sources. The AA exposure-induced DNA damage is believed to be related to both the nephrotoxicity and carcinogenicity of AA observed in patients suffering from BEN. While the chemical toxicology of AA is wellstudied, we investigated in this study the understated effect of different nutrients, food additives, or health supplements on DNA adduct formation by aristolochic acid I (AA-I). By culturing human embryonic kidney cells in an AAI-containing medium enriched with different nutrients, results showed that cells cultured in fatty acid-, acetic acid-, and amino acid-enriched media produced ALI-dA adducts at significantly higher frequencies than that cultured in the normal medium. ALI-dA adduct formation was most sensitive to amino acids, indicating that amino acid-or protein-rich diets might lead to a higher risk of mutation and even cancer. On the other hand, cells cultured in media supplemented with sodium bicarbonate, GSH, and NAC reduced ALI-dA adduct formation rates, which sheds light on their potential use as risk-mitigating strategies for people at risk of AA exposure. It is anticipated that the results of this study will help to better understand the effect of dietary habits on cancer and BEN development.

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Section: Introductionmentioning

confidence: 99%

Effects of Diet on Aristolochic Acid-DNA Adduct Formation: Implications for Balkan Endemic Nephropathy Etiology

Zhang

Chan

Pavlović

et al. 2023

Chem. Res. Toxicol.

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“…In BEN patients, it has been found that the dimensions of the kidneys depend on the parental status and the age of offspring. In the offspring of a mother with BEN, ultrasound measurements of the kidney cortex thickness seem to portend a prognostic value [ 19 ]. In conclusion, adult offspring in BEN families can be characterized by shorter kidney length and an increased excretion of albumin, total protein and β2-microglobulin, in particular, when the mother had BEN [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Balkan endemic nephropathy--current status and future perspectives

Pavlović¹

2013

Clinical Kidney Journal

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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.

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“…Data from Bulgaria [19] suggests that kidney function and size in the offspring of BEN patients are reduced before manifestation of the disease. In another investigation on the kidney size in the offspring of parents with BEN, it was noted that reduction of kidney length was related to mother's disease and that reduction of parenchyma was significant when both mother's parents had BEN and when descendants were older than 60 years at the time of the measurement [20]. …”

Section: Discussionmentioning

confidence: 99%

Values of Alpha 1 Microglobulin Does Not Differ between Individuals with and without Family History of Balkan Endemic Nephropathy

Alečković-Halilović

Mešić

Trnačević

et al. 2014

International Journal of Nephrology

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Aim. The aim of this study was to compare urinary alpha 1 microglobulin (A1MG) in healthy individuals with and without family burden for Balkan endemic nephropathy (BEN) in an endemic village. Methods. Otherwise healthy inhabitants with microalbuminuria or proteinuria were divided into two groups: with (n = 24) and without (n = 32) family BEN burden and screened for urinary A1MG and A1MG/urine creatinine ratio. Results. Average value of urinary A1MG was 10.35 ± 7.01 mg/L in group with and 10.79 ± 8.27 mg/L in group without family history for BEN (NS, P = 0.87). A1MG was higher than 10 mg/L in eight (33.33%) inhabitants with family history and in 12 (37.5%) without (NS, P = 0.187). Average values of urinary A1MG/creatinine ratio were 1.30 ± 1.59 and 0.94 ± 0.78 in group with and group without family BEN history (NS, P = 0.39, resp.). Elevated values of this ratio were found in 13 (54.17%) inhabitants with and 14 (43.75%) without family history for BEN (NS, P = 0.415). Conclusion. We did not find statistically significant difference in the examined markers between healthy individuals with and without family burden for BEN. We concluded that these markers are not predictive of risk for BEN.

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Reduced Kidney Size in Adult Offspring of Balkan Endemic Nephropathy Patients and Controls: A Prospective Study

Cited by 4 publications

References 25 publications

Effects of Diet on Aristolochic Acid-DNA Adduct Formation: Implications for Balkan Endemic Nephropathy Etiology

Effects of Diet on Aristolochic Acid-DNA Adduct Formation: Implications for Balkan Endemic Nephropathy Etiology

Balkan endemic nephropathy--current status and future perspectives

Values of Alpha 1 Microglobulin Does Not Differ between Individuals with and without Family History of Balkan Endemic Nephropathy

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