Medicinal Herb Linked to Endemic Nephropathy and Cancer

Rod Franklin

November 12, 2011

November 12, 2011 — An endemic nephropathy (EN) found in Eastern European farming communities appears to be caused by environmental exposure to the human carcinogen aristolochic acid (AA), a major component of an herb used in Chinese medicine, according to a study published online November 9 in Kidney International.

Environmental exposure to AA in the Balkans can be traced to the plant Aristolochia, which invades the wheat crops harvested in the Balkans for grain and bakery production and is also used in Chinese herbal remedies. Some people have been sickened to the point of end-stage renal disease after ingesting Aristolochia fangchi directly as part of a weight-loss regimen.

Led by Bojan Jelaković, from the School of Medicine, University of Zagreb, and Department for Nephrology, Arterial Hypertension and Dialysis, University Hospital Center Zagreb, Croatia, and coordinated through the Health Sciences Center of Stony Brook University in New York, the study focused on 77 patients living in Bosnia, Croatia, Serbia, and other Balkan regions along the Danube River, where exposure to AA is elevated.

Seeking to confirm the association between AA exposure and EN, the investigators documented the presence of 2 key biomarkers in patients from areas where nephropathy is endemic, but not in patients living in nonendemic regions.

Aristolactam–DNA adducts, formed in the renal cortex via the commingling of AA with DNA, are regarded as effective indicators of an individual's environmental exposure to AA. The adducts generate uniquely mutated signatures of the tumor suppressor gene TP53 in urothelium. These are biomarkers for AA carcinogenicity and the upper urinary tract cancers that are closely associated with EN.

When DNA was extracted from the renal cortex and urothelial tumor tissue of 67 patients (40 women, 27 men) living in regions known to harbor nephropathy in its endemic form, researchers found aristolactam–DNA adducts in 70% of the cohort (80% of the women, 56% of the men; P < 0.055). Moreover, specific A:T to T:A mutations of the TP53 gene were found in 40% of the participants from endemic regions, including 33% of the men and 44% of the women. Aristolactam–DNA adducts were found in 94% of the cases that presented with this mutation.

Neither the aristolactam–DNA adduct nor the TP53 mutation, however, was present in the tissues of 10 control patients residing in areas of non-EN.

Most of the endemic patients had lived in endemic regions for at least 20 years. Average age at the time of nephroureterectomy for removal of urinary tract carcinomas was 73.4 years. Location of the majority of tumors (70%) was either in the renal pelvis or ureter. Severe (stage 4 or 5) chronic kidney disease was evident in 38.8% of the endemic cohort. In comparison, only 20% of the nonendemic cases were classified as chronic kidney disease stage 4 or 5.

Previous investigations on the etiology of EN and upper urinary tract cancers have focused on environmental agents such as heavy metals, mycotoxins, and trace elements. The authors conclude that the current study supports the hypothesis that environmental exposure to AA is a causal factor for both EN and upper urinary tract cancers in genetically predisposed individuals.

The authors have disclosed no relevant financial relationships.

Kidney Int. 2011. Published online November 9, 2011. Abstract

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