Wake Forest Baptist receives NIH grants to study risks associated with kidney transplants

The National Institutes of Health (NIH) has awarded two five-year grants to Wake Forest Baptist Medical Center worth more than $5 million to prospectively study the effects of a genetic variation in organ donors that appears to contribute to survival of kidneys after transplantation.

The funding will establish the APOL1 Long-term Transplantation Outcomes Network (APOLLO) to evaluate donor and recipient apolipoprotein L1 (APOL1) renal-risk variants in all U.S. kidney transplants from African-American kidney donors to determine their effect on transplant outcomes. In addition, the post-donation health and kidney function of African-American living kidney donors will be assessed.

Kidneys transplanted from deceased African-American donors fail more rapidly compared to kidneys transplanted from deceased European- American donors. Reasons for this are unknown, but retrospective studies suggest that the presence of two APOL1 renal-risk variants in the African-American kidney donors may contribute to the disparity.

These gene variants are common in populations with recent African ancestry, such as African-Americans, where they are strongly associated with non-diabetic end-stage kidney disease, but rare in other racial or ethnic groups. Up to 40 percent of end-stage kidney disease in African Americans is related to variation in this gene.

"Compiling APOL1 data may provide physicians with a more accurate way to assess the likelihood for long-term renal function in transplanted kidneys," said nephrologist Barry I. Freedman, M.D., John H. Felts, III, Distinguished Professor of Internal Medicine, at Wake Forest Baptist and a principal investigator at the Wake Forest Baptist APOLLO coordinating center. "Hopefully, it also will improve our ability to match donor kidneys with potential recipients to improve the success rate of kidney transplants and patient survival."

As the national coordinating center for the APOLLO consortium, Wake Forest Baptist will be closely aligned with the United Network of Organ Sharing, the Association of Organ Procurement Organizations and 13 APOLLO clinical trial centers. Co-principal investigators of the APOLLO coordinating center are David Reboussin, Ph.D., Robert Stratta, M.D., and Donald Bowden, Ph.D., of Wake Forest Baptist.

Pioneering studies led by Freedman demonstrated that two copies of the APOL1 gene in African-American kidney donors were associated with more rapid failure of transplanted kidneys.

In addition, the NIH funding supports an APOLLO clinical center led by Amber Reeves-Daniel, D.O., of Wake Forest Baptist, and Rasheed Gbadegesin, M.D., of Duke University Medical Center. This clinical trial site, with its 12 counterparts around the country, will assist in developing the protocol and recruiting participants for APOLLO.

"Findings from the APOLLO study have the potential to alter clinical practice by increasing the numbers of kidneys available for transplantation and improving matching of kidneys with recipients to extend post-transplant kidney function," Freedman said.

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