A MEDICAL MYSTERY
“Balkan endemic nephropathy” is now called aristolochic acid nephropathy,
in recognition of the poisonous herb. The discovery of the botanical connection
has explained many cases of renal failure in other cultures—the mysterious ill-
ness was not unique to the black houses of Croatia.
he abandoned buildings stained with creeping dark mold
are called “black houses” in the Croatian villages. They once
housed farm families wiped out by a mysterious illness.
Typically a mother would sicken first, perhaps not noticing
the initial fatigue, insomnia, and frequent urination, eventu-
ally dying of renal (kidney) failure. Her husband would soon follow, and then
the children would leave, but within months or years would become ill too.
People fortunate enough to receive medical care discovered that they had
anemia, hypertension, and protein in the urine, indicators of kidney damage.
Some villages had many sick people; others didn’t. The pattern did not seem
to indicate inheritance. A family would typically vanish in three to F
as the disease took its toll.
Doctors noticed the disease in the 1950s, calling it Balkan endemic
nephropathy, in honor of its apparent origin in the northern Balkan penin-
sula. Romania, Bulgaria, Serbia, and Bosnia also had cases. Investigators ruled
out various causes: viruses, heavy metals, tainted water, fungus, weeds. Local
doctors preserved the damaged organs of their patients, in the hope that
someday the specimens might be useful in developing a treatment. The ill-
ness was devastating. At death, the kidneys were about a third the size of
normal kidneys and F
brous, and often the tubes leading from them to the
bladder were lined with tumors.
The clue that solved the mystery of the black houses came in 2000,
when a prominent medical journal reported that a Chinese herb (
) taken for weight loss caused symptoms remarkably similar to
those of the Balkan disease. Long-term use of the herb damaged delicate
kidney tissues (interstitial F
brosis) leading to renal failure, as well as caus-
ing cancer of the urinary tract lining. A biochemist at Stony Brook University,
Arthur Grollman, alerted Croatian colleagues to the possible link between
the disease and the herb, and soon additional clues turned up. Horses that
ate hay on which the herb grew developed renal failure, and the herb fed to
rats and rabbits turned their kidneys F
By this time, people with the illness in the Balkans were being treated
with dialysis, which slowed disease progression. When researchers showed
them photographs of the herb, the patients recognized it immediately—a
weed, called Wolf’s Paw, that grew on their wheat. ±urther analysis revealed
that the herb produces a pair of powerful toxins that home in on the kidneys,
causing fibrosis as well as entering cells and binding to a cancer-causing
gene called p53.
Kidney failure from a popular herb. A mysterious illness that cripples the
urinary system was F
rst described among villagers in Croatia who grew wheat.
which grew on the wheat, is also used as an herbal
A major part of homeostasis is maintaining the composition,
pH, and volume of body ﬂ
uids within normal ranges. The
urinary system accomplishes this task. It removes metabolic
wastes and chemicals in excess, yet at the same time is sen-
sitive enough so that the body is not depleted of essential
substances. The urinary system also excretes foreign sub-
stances, such as drugs and their metabolites that can be toxic
if they remain in the body ﬂ
uids after they have exerted their
The urinary system consists of a pair of glandular kidneys,
which remove substances from the blood, form urine, and help
regulate certain metabolic processes; a pair of tubular ureters,
which transport urine from the kidneys; a saclike urinary blad-
der, which collects urine from the ureters and serves as a urine
reservoir; and a tubular urethra, which conveys urine to the
outside of the body.
show these organs.