A New Marker for Kidney Disease

Bloomberg School researchers have identified genetic markers that can help explain why some people suffer kidney failure and others do not. The markers are gene variants that are highly associated with end-stage renal disease (ESRD), a chronic condition in which 90 percent of kidney function is lost, and that is treated by either dialysis or transplantation. The condition affects almost half a million Americans.

Although diabetes is the number one risk factor for chronic kidney disease, there are many non-diabetic individuals who develop ESRD, and it was in these patients that the gene variants are significantly prevalent. The analysis, led by Linda Kao, associate professor of Epidemiology, also found that the variants identified in the MYH9 gene occur with more frequency in genomes with West African ancestry, compared to genomes with white or Asian ancestry.

In fact, of the African Americans who have non-diabetic ESRD, 60 to 70 percent have these gene variants. In the control group of African Americans without ESRD, 40 percent have the marker. Compare this to the prevalence of the marker among whites in the general population: about 2 percent.

The study "addresses an incredibly important public health question: why do African Americans have higher incidence of kidney disease in the U.S.?" says Michael J. Klag, MD, MPH '87, Bloomberg School dean and the initial principal investigator for the study's recruitment grant. "This gene variant may account for a lot of the disparities. We have to figure out what in the environment interacts with this gene to create this risk of kidney disease."

Kao, PhD '99, MHS '97, emphasizes that the susceptibility variant is colorblind: a white or Asian person with the causal gene variant will be just as likely to develop ESRD as an African American with the causal gene variant. But as with other genetic markers, such as the mutations found in BRAC-1 and BRAC-2 for breast cancer, which occur more frequently in Ashkenazi women, the MYH9 variants identified in this study are more commonly observed in individuals of West African ancestry.

Study co-authors Rulan S. Parekh, MD, associate professor at the School of Medicine, and Lucy Meoni, ScM '82, project director, believe the discovery will prompt future studies aimed at better understanding the biology of kidney disease progression. Ultimately it may direct drug therapy and potential screening of patients.

The next steps for Kao and colleagues: sequencing the MYH9 gene to identify the causal variant and a similar but larger-scale genome-wide association study to identify additional susceptibility genes for kidney failure. While this study examined 1,536 markers scattered across the entire genome in order to isolate this one marker for ESRD, the new study would examine more than 1 million markers in order to query the genome in a more comprehensive manner. "We have not found all the susceptibility genes for chronic kidney disease and kidney failure," says Kao. "There are multiple genes and multiple environmental factors that are contributing to these complex conditions."