New research conducted by the National Institutes of Health (NIH) funded H3Africa Kidney Disease Research Network (H3AKDRN)—co-led by Dwomoa Adu (University of Ghana, Accra, Ghana)—has shown that APOLIPOPROTEIN L1 (APOL1) gene variants lead to an increased risk of chronic kidney disease (CKD) among Africans and people of African descent. Adu spoke to Renal Interventions, sharing his thoughts on the research and the possible next steps to address the burden of CKD in Africa.
What prompted the H3AKDRN to begin researching the impact of APOL1 gene variants on the prevalence of CKD in Africans, Adu stated, was the high rate of CKD found in African and African Caribbean populations in the UK. Further, the US Renal Data System in 2019 found that African Americans had a 3.7 times higher age adjusted risk of CKD when compared with European Americans. The prevalence of CKD in Africans was 14%, with Africans succumbing to end-stage kidney disease (ESKD) between 20–30 years earlier than Europeans. In Europe the prevalence of CKD varied from 3.31% in Norway to 17.3% in Northern Germany. Adu also added that, for many patients living in African countries, renal replacement therapy is either unavailable or unaffordable, which makes the development of ESKD “a death sentence”.
Previous studies have shown that two mutations in the APOL1 gene were associated with ESKD and CKD in African Americans. This, coupled with the fact that CKD and ESKD are so prevalent in Africans and African-descended people in the UK, USA, and in countries such as Ghana and Nigeria, suggested to Adu that “if [African Americans] had genes that make them more prone to kidney disease, they must have brought them from Africa”.
The APOL1 gene, Adu outlined, developed to fight African trypanosomiasis—also known as sleeping sickness—meaning that individuals who had the APOL1 gene survived the condition. “Their offspring,” Adu averred, “therefore rose to a higher proportion in Africa, and that protected them against sleeping sickness, which was great, but in those days, people didn’t live much beyond 30 years of age. It was only some 14 years ago that it was found that these genes, which were known to be present in Africans, were actually associated with [CKD].”
One of the aims of this study, Adu explained, was to base the genotyping in the countries in which the research was being conducted. “There have been a lot of advances in genomic studies, but these have always either been in Europe, America, Asia, or investigators from these areas come to Africa to collect a thousand samples, and then do the genomic studies back in their country of origin,” he stated. Instead of the genotyping taking place elsewhere, the H3AKDRN was able to set up two laboratories—one in Ghana and another in Nigeria—in which some of the genotyping was done.
The study, which was recently published in The New England Journal of Medicine (NEJM), was able to recruit 8,355 individuals (5,578 subjects with CKD or glomerulonephritis and 2,777 healthy controls from both Ghana and Nigeria) across 13 sites (two in Ghana, 11 in Nigeria). Blood and urine samples were collected from these subjects and some of them had a kidney biopsy.
What Adu et al found was that, in the entire study population, 29.7% had two copies of the gene of the APOL1 gene and 43% had one copy of the gene. They also found that compared with patients with no gene, one copy of the gene increased the risk of kidney failure by 18%, almost by a fifth, and two copies of the APOL1 gene increased the risk of kidney disease by a quarter (25%).
There are, however, ways in which this increased risk of CKD can be addressed. “A company called Vertex,” Adu continued, “has developed a drug—Inaxaplin—that would block APOL1 variants.” Preliminary data published in NEJM showed that patients treated with Inaxaplin had a geometric percent change from baseline urinary protein-to-creatinine ratio of -47.6 (-47.7 in participants with nephrotic-range proteinuria and -47.5 in those with subnephrotic-range proteinuria) after 13 weeks.
With this new research offering “hope for the future”, as Adu framed it, the next steps for the H3AKDRN are focussed on continuing to develop their “robust framework for the study of the genomics of kidney disease in Africa”, along with the development of future studies which will target treatment modalities of kidney diseases.
