Genetic Risk Factors for Chronic Kidney Disease Identified in New England Journal of Medicine Study

A groundbreaking study published this week in the New England Journal of Medicine reveals that a single genetic variant in the APOL1 gene significantly raises the risk of chronic kidney disease, particularly among individuals of West African descent. The study’s findings underscore the urgent need for increased awareness of genetic risk factors and early intervention strategies in kidney health.

The research, led by Dr. Akinlolu Ojo, executive dean at the University of Kansas School of Medicine, was conducted in collaboration with scientists from the National Institutes of Health (NIH) and the Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network. The study examined over 8,000 participants from Ghana and Nigeria, with nearly 5,000 confirmed cases of chronic kidney disease through kidney biopsies, providing unprecedented data on APOL1 risk variants within West African populations.

Dr. Ojo highlighted the discovery that a single APOL1 kidney risk allele—contrary to previous studies that suggested two alleles were necessary—increases susceptibility to chronic kidney disease and focal segmental glomerulosclerosis, a rare and severe kidney condition marked by kidney tissue scarring. “The increased odds of chronic kidney disease with one APOL1 risk allele could mean the risk group is one- to two-fold higher than previously thought,” said Dr. Ojo. If confirmed in African American populations, these findings may reshape current understanding and screening practices for kidney disease.

Chronic kidney disease (CKD) is often referred to as a “silent killer,” progressing without noticeable symptoms in its early stages, and affecting one in seven adults in the U.S. alone, according to recent estimates. While African American, Hispanic American, and Native American communities are disproportionately affected, people with diabetes or hypertension also face a higher likelihood of developing CKD, which impairs the kidneys’ ability to filter blood effectively. As CKD advances, it disrupts essential bodily functions like red blood cell production and calcium regulation, potentially leading to serious complications, including heart attacks and strokes.

Dr. Adebowale A. Adeyemo, deputy director and chief scientific officer at NIH’s National Human Genome Research Institute and co-author of the study, emphasized the global significance of the findings. “Our study provides data about West Africans that will help us better understand the risk of chronic kidney disease associated with APOL1 variants,” he explained. “By comparing this study to previous findings in African American populations, we can deepen our understanding of the impact of these high-risk APOL1 variants.” Adeyemo added that such genetic information could empower individuals to make more informed health decisions and encourage earlier intervention.

Findings from the study reveal that nearly one-third of individuals in Ghana and Nigeria carry the APOL1 risk variant, heightening their susceptibility to CKD. While these variants are most prevalent in individuals of West African heritage, they also appear among people from Europe, Asia, and Central and South America, demonstrating the necessity of diverse population studies for accurate genomic insights. “This research underscores the importance of studying diverse populations,” Adeyemo noted. “By doing so, genomic medicine can be applied equitably across different communities worldwide.”

Surprisingly, the study found that one APOL1 risk allele alone could increase CKD risk by 18%, while two alleles increased it by 25%. This result contrasts with earlier studies involving African Americans, which suggested that two copies of the risk variant were required to raise susceptibility, highlighting a need for further research.

Dr. Paul Kimmel, a co-author of the study and program director at the National Institute of Diabetes and Digestive and Kidney Diseases, stressed the potential impact of this research on U.S. populations. “Further research with U.S.-based participants will help us understand how APOL1 variants affect kidney health,” said Dr. Kimmel. “We hope these insights will lead to improved health outcomes for individuals at risk or suffering from kidney disease.”

As the global understanding of genetic risk for CKD deepens, researchers hope that such studies will help develop better screening, treatment, and prevention methods, bringing new hope to individuals worldwide at risk for this chronic, often silent disease.