An Israeli research team, headed by Rambam nephrologist, Prof. Karl Skorecki, working in collaboration with U.S. counterparts, has made a revolutionary discovery. The scientists have revealed new genetic data on a DNA region that could predict who might be at greatly increased risk for developing kidney disease. This discovery promises to help millions of people, particularly those of African descent, who have two to four times the risk for the illness compared to Caucasians of European origin.

Approximately forty million individuals in the US have chronic kidney disease at various stages of severity. Some half a million Americans and 5,000 Israelis have end-stage disease, requiring life-sustaining dialysis or transplantation. While these therapies sustain life, they can reduce its quality and increase mortality. In places where dialysis and transplantation are not available, end-stage kidney disease is fatal.

In the current issue of the prestigious journal Human Molecular Genetics, a research team led by Rambam Health Care Campus Professor Karl Skorecki and Dr. Doron Behar, and comprised of researchers from Rambam, the Technion – Israel Institute of Technology, Hadassah Medical Center, Tel Aviv University, and the US National Institutes of Health reported a strong association of new markers within the MYH9 gene, which encodes a tiny sub-cellular nanomotor protein in the kidney, with common forms of end-stage kidney disease in different population groups. The researchers found a particular group of markers that designate a variant of the gene, which appears to have originated in Western and South Africa. This gene variant also carries a high risk for kidney disease, when present in mixed populations, such as Hispanic Americans. Today, this risk is reflected in African-Africans, who have four times the risk for the fatal disorder, while those of Hispanic origin have twice the risk.

This finding represents one of the highest-ever reported genetically-based set of risk markers for a common disease. It indicates that markers for population health screening can be useful in preventing kidney disease. In addition, these markers may help in identifying the actual genetic mutation and abnormality in the nano-motor protein that it encodes, which promotes kidney disorders. In turn, this discovery may open the way for the eventual development of preventive and therapeutic interventions.

Until recently, the medical community thought genetic factors played a relatively minor role in just a few rare forms of kidney disease. Recently, however, researchers have noted great disparities in the prevalence of the most common forms of end-stage kidney disease among different population groups in North America. This suggests that genetic factors may be significant in almost all forms of the illness, especially among African-Americans and Hispanic-Americans.

The observation that these disparities could not be attributed solely to socio-economic, cultural,
dietary, or environmental factors indicated a major genetic contribution to common forms of kidney disease – and motivated this research project. This was further strengthened by a finding of Prof. Skorecki and colleagues: Ethiopians, as compared to their West and South African neighbors, do not share the same increased risk of kidney failure.