Herbal 'remedy' may trigger widespread kidney failure

— -- Kidney stones. Snakebites. Head wounds. To the ancients, a weed called birthwort was a wonder drug that treated them all, and more.

Medical detectives, however, are finding that the ancient remedy likely has caused centuries of kidney failure and cancer, as well as being the culprit in a widespread syndrome of kidney disease in some parts of the world.

"The big clue was the plant itself," says pharmacologist Arthur Grollman of Stony Brook (N.Y.) University. "Once it was appreciated that it contained a potent kidney toxin and human carcinogen, we could get to the bottom of things."

Grollman and colleagues have unraveled a genetic signature left behind by birthwort in cases of cancers and kidney failure, as reported in the March journal ofKidney International. And in upcoming work, they report signs that use of the drug in Chinese medicines may be responsible for Taiwan's sky-high rate of kidney disease.

Over a century ago, toxicologists first recognized harmful properties of aristolochic acid, found in the Aristolochia (Ah-wrist-oh-LOW-key-ah) plant family that includes hundreds of species of birthworts (sometimes called "Dutchman's pipes" for the long curved shape of their flowers). The knowledge caused little medical concern about the herb, which produces dirty yellow to red flowers and had been catalogued since at least 300 B.C., by one of Aristotle's students as an herbal remedy.

In 1969, however, a Croatian researcher first noted that Aristolochia poisoning may play a role in unusual kidney failure and urinary tract cancer cases afflicting farming villages along the Danube River valley in Croatia, Bulgaria, Romania and elsewhere in the region. Only about 700 villages suffered from "Balkan endemic nephropathy" and families suffered the syndrome in a patchy way, suggesting an environmental explanation. Based on observations that birthwort grew thickly in and around the wheat that farmers grew, researchers began to suspect that they were baking birthwort seeds in their bread, which concentrate aristolochic acid. However, there were many other explanations for the syndrome as well to check, ranging from pollution to fungal contamination of grain, so the idea lay fallow.

Modern medicine became alarmed by birthwort in 1991, when dozens of young women from a "slimming" clinic in Brussels, Belgium, appeared in doctor's offices with kidney failure. The case triggered warnings and a 2000 New England Journal of Medicine report noting that about 5% of 1,800 women given the Chinese herb, Aristolochia fangchi (another birthwort species), in a weight-loss treatment at the clinic had developed kidney failure. That triggered a Food and Drug Administration warning about the herb that mentioned 16 weight-loss products then on store shelves, and also offered a clue that only some people suffered from a genetic susceptibility to the herb causing kidney failure, Grollman says.