Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Sep;34(9):1688-705.
doi: 10.1111/risa.12239. Epub 2014 Jun 20.

Evaluating weight of evidence in the mystery of Balkan endemic nephropathy

Travis Bui-Klimke  1 , Felicia Wu
Affiliations

Evaluating weight of evidence in the mystery of Balkan endemic nephropathy

Travis Bui-Klimke et al. Risk Anal. 2014 Sep.

Abstract

Balkan endemic nephropathy (BEN) is a chronic, progressive wasting disease of the kidneys, endemic in certain rural regions of the Balkan nations Croatia, Serbia, Bulgaria, and Romania. It is irreversible and ultimately fatal. Though this disease was first described in the 1950s, its causes have been a mystery and a source of much academic and clinical contention. Possible etiologic agents that have been explored include exposure to metals and metalloids, viruses and bacteria, and the dietary toxins aristolochic acid (AA) and ochratoxin A (OTA). AA is a toxin produced by weeds of the genus Aristolochia, common in Balkan wheat fields. Aristolochia seeds may intermingle with harvested grains and thus inadvertently enter human diets. OTA is a mycotoxin (fungal toxin) common in many foods, including cereal grains. In this study, we analyzed the weight of evidence for each of the suspected causes of BEN using the Bradford Hill criteria (BHC): nine conditions that determine weight of evidence for a causal relationship between an agent and a disease. Each agent postulated to cause BEN was evaluated using the nine criteria, and for each criterion was given a rating based on the strength of the association between exposure to the substance and BEN. From the overall available scientific evidence for each of these suspected risk factors, AA is the agent with the greatest weight of evidence in causing BEN. We describe other methods for testing causality from epidemiological studies, which support this conclusion of AA causing BEN.

Keywords: Aristolochic acid; Balkan endemic nephropathy; Bradford Hill criteria; ochratoxin A; weight of evidence.

PubMed Disclaimer

References

    1. Polenakovic M, Stefanovic V. Balkan nephropathy Pp. 857‐866 in Cameron JS, Davison AM, Grunfeld JP, Kerr D, Ritz E. (eds). Oxford Textbook of Clinical Nephrology, 1st ed. Oxford, UK: Oxford University Press, 1992.
    1. Craciun EC, Rosculescu I. On Danubian endemic familial nephropathy (Balkan nephropathy). Some problems. American Journal of Medicine, 1970; 49(6):774–779. - PubMed
    1. Tanchev I, Ts E, Dorosiev D, Zh P, Tsvetkov G. [Study of nephritis in Vrattsa district]. Suvremenna Meditsina (Sofiia), 1956; 7(9):14–29. - PubMed
    1. Batuman V. Fifty years of Balkan endemic nephropathy: Daunting questions, elusive answers. Kidney International, 2006; 69(4):644–646. - PubMed
    1. Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, Jakovina K, Brdar B, Slade N, Turesky RJ, Goodenough AK, Rieger R, Vukelic M, Jelakovic B. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(29):12129–12134. - PMC - PubMed

Publication types

LinkOut - more resources