Kidney disease, which can lead to kidney failure, affects black populations at a significantly higher rate than white populations. This disparity results in a heavy burden of healthcare costs, particularly among people of African descent worldwide. In the United States, for example, black individuals make up only 13 to 14 percent of the total population but account for one-third of patients with end-stage kidney disease requiring dialysis or transplantation.
Hypertension, diabetes, and HIV, all of which contribute to kidney failure, tend to cause more severe damage and progress more rapidly in black individuals. For decades, researchers sought to understand why these differences existed. In recent years, genetic studies have provided answers, revealing that a specific genetic variation, APOL1, plays a significant role.
This genetic variation originally evolved as a defense against trypanosomiasis, commonly known as sleeping sickness, which was widespread in West Africa. The gene causes the immune system to produce a protein that attacks the parasite. However, as the parasite developed resistance, new gene variants APOL1 G1 and G2 emerged to counteract the threat. While these variants helped protect against disease, they also carried an unintended consequence: an increased risk of kidney disease.
Over the last two decades, evidence has shown that these variants contribute to kidney disease among African Americans, even in the absence of diabetes. However, until recently, the connection between the APOL1 gene and kidney disease had not been thoroughly studied among Africans on the continent, where the gene first evolved.
To address this gap, a major study was launched more than a decade ago, involving researchers from Nigeria, Ghana, South Africa, Ethiopia, and Kenya. The research aimed to examine 8,000 cases and conduct genetic studies related to kidney disease. A team of more than 40 specialists, including nephrologists, geneticists, and laboratory scientists, collaborated on the project.
The study enrolled 8,355 participants from Nigeria and Ghana, with 4,712 diagnosed with kidney disease and 2,777 without the condition. Sophisticated genetic analyses were conducted on samples obtained from participants, revealing crucial insights.
Findings showed that APOL1 gene variants are more common in West African populations than in other parts of Africa. Among participants, 43 percent carried one variant, while 29.7 percent had two copies of the high-risk variants (either G1 or G2). Those with two copies were significantly more likely to develop chronic kidney disease than those with one, and those with one variant were at higher risk compared to those with none.
These findings confirmed what had been observed in African Americans: the genetic basis for the increased risk of kidney disease among people of African descent.
This research paves the way for several advancements. One major implication is the potential to improve kidney transplant outcomes by screening donors for high-risk APOL1 variants. Additionally, targeted treatments can be developed for individuals with these variants.
A promising new drug, Inaxaplin, has been shown to inhibit APOL1 function and reduce proteinuria, a key marker of kidney disease. This raises the possibility of effective treatments for patients with APOL1-associated chronic kidney disease. Ongoing studies continue to explore further therapeutic options, offering hope for better prevention and management of kidney disease in populations with high-risk genetic variants.
