Kidney disease, leading to kidney failure, afflicts disproportionately more black people than white people, resulting in a huge burden of kidney healthcare costs among black people all over the world.
Now, findings from recent research could lead to improvements in screening for risk of kidney disease, reveal more about how it affects west Africans, in particular, and result in treatment opportunities, write Samuel Ajayi and Yemi R Raji from the University of Ibadan, Nigeria, in The Conversation.
They write:
In the US, although the black population is only 13% to 14% of the total, black people account for one-third of the patients with end-stage kidney disease requiring dialysis or transplantation.
Hypertension, diabetes and HIV, which also cause kidney failure, tend to cause more severe kidney damage and rapid deterioration in black people than in white people.
For many decades, researchers wondered why these differences exist. It was only in the past decade and a half that reasons became clearer.
Research found that black people have a genetic variation which emerged to protect the body from a parasitic disease called trypanosomiasis, or sleeping sickness.
This disease was common in the west African region. The gene prompts the immune system to produce a protein that dissolves the membrane of the parasite, destroying it.
Over time, the parasite developed resistance to the gene variant’s effects. Then new variants emerged to restore immunity against the newer forms of the parasite. But this came with a drawback: individuals who have the new gene variants (called APOL1 G1 and G2) also have an increased risk of developing kidney disease.
Over the past two decades there has been growing evidence that these variants cause kidney damage in African Americans, even if they don’t have diabetes.
However, until recently, this link between the gene and kidney disease had not been confirmed or fully described among people on the African continent – where the genetic variant first evolved.
This was the aim of a study that began more than a decade ago in Africa, called Human Heredity and Health in Africa (H3Africa), by the Kidney Disease Research Network.
As part of this effort, our recently published study in New England Journal of Medicine found that having APOL1 G1 or G2 significantly increased the risk of having kidney disease compared with those who do not have the gene variants.
This could lead to improvements in screening for risk of the disease and about how kidney disease affects west Africans in particular, and hopefully, result in treatment opportunities.
The current prevalence of kidney disease is 13.7% in Nigeria and 28% among Ghanaians.
Our research
The Kidney Disease Research Network assembled researchers in Nigeria, Ghana, South Africa, Ethiopia and Kenya. Among the aims of the research were to study and describe 8 000 cases and controls, and conduct genetic studies associated with kidney diseases. More than 40 researchers collaborated on the project, including nephrologists, geneticists, genetic statisticians and laboratory scientists.
The study enrolled 8 355 participants in Ghana and Nigeria, including 4 712 with kidney disease of varying severity and 2 777 without kidney disease. Extensive and sophisticated genetic studies were done on the materials obtained from the participants with their consent.
The gene variants that could cause kidney disease are called APOL1 G1 or G2. The variant that does not cause kidney disease is called G0. Individual people can have different combinations of these three variants.
We found that the APOL1 genes are more common among west African populations, including Nigerians and Ghanians, than among populations from other regions of Africa.
In our study, 43% (3,592) participants had just one of the variants, while 29.7% (2,481) participants had double variants of APOL1.
Participants with double G1 or G2 variants were more likely to have chronic kidney disease than those with one of those variants. And participants with one variant were more likely to have chronic kidney disease than those who had none.
Our study thus confirmed what was found in people of African descent in the US: the genetic origin underpinning the excess risk of developing kidney disease among black Africans, wherever they live.
What our findings mean
The study established, for the first time, the association of APOL1 with chronic kidney disease in sub-Saharan Africa.
This opens up opportunities:
• improving the survival of kidney transplant patients by screening donors who may have the high-risk variants; and
• targeted treatment of those with high-risk variants.
A new drug, Inaxaplin, which inhibits APOL1 function, reduces proteinuria, the hallmark of kidney disease. This opens the possibility of treating patients with APOL1 mediated chronic disease with medications. Studies are continuing in this area.
Samuel Ajayi, Reader, College of Medicine, University of Ibadan; Yemi R. Raji, Associate Professor of Medicine and Consultant Nephrologist, University of Ibadan.
Study details
APOL1 Bi- and Monoallelic Variants and Chronic Kidney Disease in West Africans
Rasheed A. Gbadegesin, Ifeoma Ulasi, Samuel Ajayi, Yemi Raji, Timothy Olanrewaju et al.
Published in New England Journal of Medicine on 26 October 2024
Abstract
Background
Apolipoprotein L1 gene (APOL1) variants are risk factors for chronic kidney disease (CKD) among black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the black population.
Methods
We conducted a case–control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analysed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex.
Results
Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis.
Conclusions
In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)
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