Aristolochic acid, a plant component used in herbal remedies, appears to lead to kidney failure and urothelial cell carcinomas (UCC) in individuals exposed to the toxin, an international group of researchers reports.
For their study, co-author Arthur Grollman, MD, of Stony Brook University School of Medicine, Stony Brook, NY, and an international team of scientists examined patients in Croatia, Bosnia, and Serbia with the unusual kidney disease known as Balkan endemic nephropathy.
Six years ago, Dr. Grollman and his team initiated studies based on the hypothesis that exposure to the toxin in endemic areas was the result of ingestion of contaminated wheat grain.
"Results of our study indicate that dietary exposure to aristolochic acid in this population is causally related to endemic nephropathy and carcinomas of the upper urinary tract in genetically susceptible individuals," Dr. Grollman said. "Implications of these results go beyond the population of those exposed in the Balkans, as millions of people worldwide are at risk for developing diseases due to aristolochic acid exposure from traditional remedies prepared from Aristolochia herbs.
"More broadly, we believe that aristolochic acid nephropathy and urothelial cell carcinoma represent a long-overlooked global disease and an international public health problem of significant magnitude."
The authors found aristolactam (AL)-DNA adducts in the kidney cortex of 70% of the endemic UCC patients and in 94% of patients who carried "fingerprint" mutations in TP53. Neither the AL-DNA adducts nor the fingerprint TP53 mutations were detected in DNA extracted from tissues of UCC patients who lived outside the region.
"These findings demonstrate that the presence of AL-DNA in the kidney cortex, together with the specific mutations in tumor tissue, are biomarkers of exposure to aristolochic acid," Dr. Grollman said. "This molecular epidemiologic study provides evidence not only that genetically susceptible individuals exposed to the toxin likely will develop the disease, but also provides a solid foundation for public health officials to develop strategies designed to eliminate endemic nephropathy. In addition, the research provides the means to further investigate the causes of related kidney diseases and urothelial cancers in countries where Aristolochia plants are used in traditional herbal medicines."
Among the 77 UCC patients studied in the Balkans, 67 of them lived in the endemic region for at least 20 years. The overall prevalence of chronic kidney disease in both the UCC endemic and nonendemic cases was similar, affecting 84% and 90% of the patients, respectively. All but two individuals from the endemic population reported cultivating and harvesting their own wheat 20 to 30 years ago.
Results from the study were published online in Kidney International (Nov. 9, 2011).
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