Clerkship in Croatia

In 2004, Tjaša Hranjec stopped by Arthur Grollman's office at Stony Brook University in New York. Heading into her second year of medical school, Hranjec wanted to do research. Grollman asked about her accent, and, after she told him she was Croatian, hired her on the spot. "He said, 'Do I have a project for you!'" she says, laughing. "It was coincidence, or fate."

Now a University of Virginia surgical resident, Hranjec spent the summers of 2004 and 2005 in Slavonski Brod and coauthored the first case-controlled epidemiologic study on endemic nephropathy, aided by a Croatian initiative called perlustracija.¹ Every other year or so, except when the war intervened, health investigators visit a cluster of endemic villages to track the numbers of endemic nephropathy deaths and diagnoses and to screen for warning signs of the disease.

Bearing a lengthy questionnaire and the perlustracija list of patients in each village, Hranjec learned that in Croatia Aristolochia clematitis and wheat go to seed at the same time. She also learned that endemic nephropathy patients in Slavonski Brod baked bread from grain they'd grown themselves or bought flour milled from local wheat. The methods for sieving the grain failed to remove all the A. clematitis seeds before it was milled, even after the farmers exchanged their scythes for combines and their village mills for mechanized ones in the 1980s. "Some of the villagers in Kaniža remembered that the bread tasted bitter when there were too many weeds in it," she says, adding that bread constitutes at least half of their diet.

From Hranjec's work sprang the hypothesis that the Grollman team successfully tested in its three-pronged study, published in July in the Proceedings of the National Academy of Sciences: The villagers have been harvesting wheat grain and A. clematitis seeds simultaneously for generations and poisoning themselves with bread made from the contaminated flour.²

Josip Olujević left the endemic village of Banovci when he was 15. His mother and father later died of the disease, along with a sister, cousin, and several neighbors. A second sister and his brother were spared. In 1991, when Olujević was 46, he was diagnosed. The retired agricultural engineer's arms bore the ropy veins and long scars associated with dialysis, and his skin was pale yellow when he arrived at the clinic on a recent morning carrying a bag of apples and a small leather satchel.

Through a translator, he says his mother baked bread from the grain his father cultivated and, after he left the village for school, she sent him some loaves, weighing 3 to 4 kilos apiece, every month. It was good bread, he says, and he paid no attention to the flecks of vučja stopa seeds in it.

"I don't know about this new theory of the bread," Olujević says, recalling that investigators came to Banovci when he was a boy to take samples from his family's slaughtered pigs to test for a virus. "There were many theories and I remember a lot of them." Then he adds, with an impatient wave of an arm, "voda, voda." Roughly translated: They also said it was the water.

Olujević's wife and three children were never exposed, making it likely that he will be the last of his family to die from endemic nephropathy. Ninoslav Leko, his nephrologist, says that among the 400 people now living in Banovci, 10 families have an ongoing history of endemic nephropathy.