Doctors aren't completely sure why African Americans are more prone than white Americans to kidney disease and failure.  Nephrologist Duncan Johnstone says for decades the difference was often blamed on patients.

"That's happened a lot in the history of medicine and African Americans. 'It's their diet, it's their lifestyle'--all of these judgments against them," said Johnstone, a physician-researcher at the University of Pennsylvania.

About 29 percent of all people treated for kidney failure in the U.S. are African American. In comparison, about 14 percent of the overall population is black. When the kidneys fail that change requires a new life on dialysis and an often years-long wait for a kidney transplant. Scientists are still looking for answers in lifestyle choices and access to health care, but researchers say genetics is a clue too.

"Instead of saying 'Oh, you're African American you're at high risk of kidney disease.' We can move beyond racial stereotyping, if you will. We can say this particular person is at high risk for kidney disease and this person is not," said Martin Pollak, chief of nephrology at Beth Israel Deaconess Medical Center in Boston.

Biological information inside a cell acts like marching orders to our genes. That set of genetic instructions is called the genome. In 2008, scientists analyzed the genome looking for an explanation for the spiked kidney disease risk among African Americans. Genes are packed into a long string of molecules call a chromosome. In early analyses a small region on chromosome 22 stood out.

"That first analysis gave us a general location for the part of the genome that's responsible for differences. It's like saying: Somewhere in Philadelphia, or somewhere in Los Angeles, there's something of interest," Pollak said.

"We had the right zip code, but didn't have the right house. We now think the right house is APOL1," Johnstone said.

Pollak's team and others refined earlier research and discovered two tiny differences in the coding sequence of a gene called APOL1. The variants are called G1 and G2. Their presence--or absence--seems to explain much of the black-white difference in kidney disease rates, Pollak said.

"We don't see these variants in anyone anywhere expect those with recent African ancestors," he said. "We've looked in European Americans, we've looked in the Middle East, we've looked in India, we've looked in China."

Identifying the variants is just part of the story behind African Americans' susceptibility to kidney disease and APOL1. Scientists suspect that the gene differences evolved over thousands of years to fight off a neurological illness common in Africa. Pollak says the variants boost the body's resistance to a blood-born parasite that causes African Sleeping Sickness.

"We think these are two pretty much unrelated things: The fact that it kills the parasite, which is obviously a big benefit to people, and the fact that it hurts the kidneys, which is not so good," Pollak said.

People who've inherited two copies of G1 or G2 have a very high risk for kidney disease, but not all African Americans have the variant. Pollak says perhaps 10 to 15 percent of African Americans have the very high-risk genotype.  That's three and a half to four million U.S. blacks. While there's an increased risk, not everyone with the gene variant goes on to develop kidney disease. Scientists aren't sure what other right--or wrong--conditions lead to illness.

"That's half of the reason it's too early to start genetic testing. We need to know more. If I were to test you and found that you had the APOL1 variant not only would I be unable to tell you, for sure, if you're going to get kidney disease, I don't know yet why that variant causes kidney disease, so I can't tell you what to do to prevent that disease from coming," Johnstone said.

Pollak's lab has developed a test and he's looking for a commercial lab to develop a screening tool.  Several physicians said they don't expect an APOL1 test to become a routine part of medical practice soon.

Tracking down the APOL1 differences lets doctors move beyond the broad-stroke characterization that "blacks are at risk for kidney disease." Still the big aim is to figure out how those genetic differences hurt kidney health and then design better treatment and prevention.

"It's a great goal," Johnstone said. "That would mean a lot of people who are on dialysis and getting kidney transplants might not ever need those therapies. It's potentially going to effect the lives of a lot of African Americans, but there's an awful lot that we need to understand."