In 1992 a cohort of women with a rapidly progressive interstitial nephritis was identified in Belgium. The cause of this nephropathy was subsequently traced to the use of Chinese herbal medicines designed to encourage weight loss. The offending herbs were banned. Nevertheless, more than 100 cases of the disease had been reported in Belgium by 1998. The herb blamed for most of the cases was Aristolochia fangchi which is rich in aristolochic acid (AA); this compound seemed to be the cause of the disease.
Debelle and colleagues review this disorder in a paper in Kidney International. Their in depth review exhaustively covers the subject. They believe that the disorder is seriously underreported. The disease may be quite widespread in India, China, and other Asian nations. Debelle, et al list many botanicals that are suspected to contain AA. The list is so long that you might be tempted to cancel your trip to the Beijing Olympics. These authors favor the less colorful name for this disorder of aristolochic acid nephropathy (AAN) as opposed to Chinese Herbal Nephropathy.
Balkan endemic nephropathy (BEN) was a disease reported, not surprisingly, in the Balkans about 50 years ago. It closely resembles AAN.
Proposed relationship of AAN and BEN – Debelle, et al
Though its pathogenesis is unknown it may be due to wheat contaminated with seeds of Aristolochia clematitis and thus may be an earlier incarnation of AAN. AA exposure is also strongly linked to urothelial malignancies. The takeaway message here is to avoid AA. AA-containing herbal medicines are widely available in many countries and can easily be obtained over the Internet. Caveat emptor.
While I agree with the take home message to avoid herbal remedies containing high concentrations of aristolochic acid (AA), I take issue with linking AA exposure as a cause of Balkan endemic nephropathy. Although Chinese Herbal Nephropathy (CHN) superficially resembles Balkan endemic nephropathy (BEN), there are many differences. Most notably is that CHN results from acute exposure to high doses of aristolochic acid from an herbal remedy and diet fad. BEN, in contrast, is a slowly developing (20+ years) disease. Perhaps the most characteristic feature of BEN is the geographic restriction of the disease to discrete clusters of villages in the affected countries. The aristolochia hypothesis for BEN does not explain this geographic restriction, as Aristolochia is found throughout the affected countries, and indeed occurs worldwide. Maps of the distribution of Aristolochia in Romania show that the greatest abundance of the plant occurs far to the east of the BEN area.
The idea that seeds from Aristolochia (where most of the aristolochic acid is concentrated) is incorporated in the wheat is also not consistent with the facts. First, wheat is not even grown in some BEN areas because of the hilliness of the terrain. Second, in the BEN regions where wheat is grown, the wheat is harvested before the Aristolochia seed pods are fully formed. Third Aristolochia seeds are very large, and would not be easily incorporated with small wheat seeds (the farmers are very savvy about contaminating wheat seed).
The BEN area villagers do make an herbal tea from Aristolochia leaves, but this tea is also used outside of the BEN areas in the Balkans, and the tea contains nearly undetectable amounts of aristolochic acid.
In short, the hypothesis linking exposure to aristolochic acid to BEN is far from proven, and is at odds with many of the facts concerning BEN.