Duke researchers led efforts in a collaborative case control and cohort study in Ghana and Nigeria on the prevalence of genetic risk factors for chronic kidney disease (CKD). They found that having just one risk variant in the APOL1 gene can significantly increase the risk of developing CKD. Results were published in the New England Journal of Medicine.
CKD is a gradual loss of kidney function. When kidneys cannot properly filter waste and excess fluids from a person’s blood, that waste collects and builds up in the body. Overtime, it creates irreversible damage. CKD can progress to end-stage kidney failure, which is fatal without dialysis or a kidney transplant.
“This disease disproportionately affects children and adults of African ancestry,” said Rasheed Gbadegesin, MD, Wilburt C. Davison Distinguished Professor and lead author. “Black Americans have a risk of CKD four times higher than that of Americans of European ancestry.”
Over 8,000 people from Ghana and Nigeria were recruited to this study from more than 10 academic medical centers, including nearly 5,000 people with CKD in stages 2-5. “We found that among the participants,” Gbadegesin said, “nearly one-third of individuals have APOL1 variants, putting them at increased risk of CKD.”
Two African ancestry-associated genetic variants in the APOL1 gene implicated in CKD, G1 and G2, likely helped combat two forms of African sleeping sickness thousands of years ago. But now, even having one of these variants in one copy of the APOL1 gene increases the risk of developing CKD. This updates, previous findings suggesting that a person needed both copies of APOL1 gene variants to increase the overall risk.
Their results show that having one risk variant increases the risk of CKD by 18%, and two risk variants increases risk by 25%. “With this research,” Gbadegesin said, “we define the role of APOL1 variants in CKD in Africans living in Africa. We also showed that the prevalence of APOL1 high risk genotype could be as high as 50% in some populations in Africa.”
This dramatically increases the pool of patients with APOL1 associated kidney disease, which may make this group a target for future clinical trials.
Next, Gbadegesin and team will use these findings to set the stage for clinical trials of compounds targeting APOL1 in Africa and conduct additional studies to comprehensively define the genetic architecture of CKD in Africa.