The Reason Why Kidney Diseases And Kidney Failures Are More Common In Black Sub-Saharan Africans

WHY KIDNEY DISEASES ARE MORE COMMON IN BLACKS

Compared to the white population, blacks are more than 3 times as likely to have kidney failure. Here is the historical reason.

Sleeping sickness or African trypanosomiasis, was highly prevalent in the sub-Saharan African region.

African trypanosomiasis is transmitted to humans through the bites of tsetse fly. The tsetse flies acquire the Trypanosomes from infected humans and animals.

Most cases (92%) of African sleeping sickness are caused by the parasite, Trypanosoma brucei gambiense found in western and central African countries and in Uganda.

8% of cases of African sleeping sickness are caused by the parasite, Trypanosoma brucei rhodesiense, found in Eastern and Southern Africa.

THE APOL1 PROTEIN

Apolipoprotein L1 (APOL1) is a protein that circulates in the blood as the protein component of high-density lipoproteins (HDL)

APOL1 proteins provided humans with protection against trypanosomiasis. However, the 2 human-infective trypanosomes (T. b. gambiense, and rhodesiense) adopted evasive measures that helped them to escape destruction by the APOL1 proteins. So, the deadly sleeping sickness continued to harm susceptible individuals in the Sub-Saharan region of Africa.

Mutations in the APOL1 gene on Chromosome 22 generated 2 genetic variants of the APOL1gene, known as APOL1 G1 and APOL1 G2 variants.

The APOL1 gene variants (APOL1 G1 & G2) code for proteins that confer some degree of protection against human-infective trypanosomes.

Because of the protection provided by the modified genes (APOL1 G1 and G2) against trypanosomiasis, the APOL1 G1 and G2 gene frequency increased rapidly among the sub-Saharan black African population.

The APOL1 G1 and G2 variant genes occur only in populations with black African-ancestry and are inherited as recessive genes with incomplete penetrance.

In the year 2010, the 2 APOL1 variant genes became known as APOL1 kidney risk variants. This is because the variant proteins (APOL1 GI & G2) were discovered to be the major drivers of the numerous kidney diseases in the Black population.

APOL1 gene is the single most important gene associated with kidney diseases in Black people.

People of black African ancestry who are double carriers of the high-risk variants: G1/G1, G1/G2 or G2/G2 are at increased long-term risk for chronic and progressive kidney diseases.

INHERITANCE OF APOL1 GENE.

The variant genes are inherited as recessive genes. Therefore, if both parents are carriers of one variant gene, their progeny has a 25% chance of becoming a double carrier of the variant genes (G1/G1, G1/G2/ G2/G2).

It must be noted that only 15-20% of the double carriers of the variant genes develop APOL1 variant-mediated kidney diseases (AMKD). The majority (about 80%) of double carriers of the variant genes do not develop AMKD.

20-22% of African Americans carry the G1 variant in their chromosomes; 13-15% of African Americans carry the G2 variant in their chromosomes. 14% of African Americans are double carriers of the variant genes (G1/G1, G2/G2, G2/G2)

Among the Asante tribe in Ghana 41% carry the G1 variant genes, and 12.9% carry the G2 variant in their chromosomes

Among the Yorubas, 45% carry the G1 variant gene and about 10% carry the G2 variant genes.

HIGH LEVELS OF G1 & G2 PROTEINS ARE TOXIC TO CELLS AND CELLULAR ORGANELLES.

G1 and G2 proteins attach to plasma membranes of cells and create cation channels that allow influx of Na+, Ca2+ and Chloride ions. The influx of these ions leads to osmotic swelling of the cells and internal organelles. Cellular organelle dysfunction leads to inflammatory cell death and in the kidneys, podocyte damage.

In the Kidneys, the damaged podocytes detach from the glomerular basement membrane. There is loss of podocytes, and this leads to loss of proteins in the urine and the scarring of the kidney filters (glomeruli).

Kidney damage is often precipitated by viral infections that activate the release of inflammatory mediators like interferon.

BIOMARKERS INDICATING WORSENING KIDNEY DISEASE.

Since only 15-20% of double carriers with G1 and G2 variant genotype develop nephropathy, how can we tell who will develop kidney disease?

Specific blood tests are available to determine those with kidney diseases who are at increased risk for AMKD. The Biomarkers that predict nephropathy include:

1. Kidney injury molecule
2. Tumor necrosis factor receptors (TNFR) 1
3. Tumor necrosis factor receptor (TNFR) 2
4. Soluble urokinase type plasminogen activator receptor (suPAR)

Elevated plasma suPAR levels are associated with the development of chronic kidney disease in the black population. In children with existing chronic kidney disease, elevated plasma suPAR levels are associated with a more rapid decline in kidney function.

Plasma levels of kidney injury molecule 1, TNFR1, and TNFR2 can help stratify G1 and G2 carriers at risk for nephropathy.

FACTORS THAT PRECIPITATE FULMINANT KIDNEY DISEASES IN APOL1 GENE CARRIERS.

Inflammation and immune system activation increase plasma suPAR levels. Inflammatory mediators, IFN-y and TNF-alpha, increase G1 and G2 expression in the various tissues.

Viral infections:

Viral infections that trigger intense immune response and release of inflammatory cytokines like interferon and tumor necrosis factors.

The list is long; it includes

• HIV
• Parvo virus
• SARS CoV-2(Covid virus).
• Hepatitis B virus

Air pollution.

Fine particulate matter <2.5 micrometer and APOL1 are independently associated with nephropathy in people with black African ancestry.

APOL1-MEDIATED KIDNEY DISEASES (AMKD)

AMKD is the reason why Black people have much higher incidence of kidney diseases

APOL1 kidney risk variants (G1 and G2) are common in sub-Saharan Africa and the diasporas with Black African ancestry.

APOL1 mutations produce a variety of kidney diseases that manifest at younger ages in Black populations with African ancestry.

Double carriers of variant genes are placed on dialysis at a mean age that is 9 years earlier than people of African ancestry who are non-carriers of the variant genes.

45% of those being placed on dialysis under age 60 years are double carriers, compared with the 25% of non-carriers who initiate dialysis after age 60 years.

Carriers of single G1(not G2) are at risk for early onset end stage renal diseases.

In the Asante and Yoruba population of West Africa, 40-45% are single carries of the GI gene. The burden of end stage renal diseases shall continue to remain high in West Africa.

TREATMENT

Currently, there are no specific treatments for AMKD. Drug trials are ongoing. Affected persons are treated symptomatically with existing kidney-protecting medications.

What we can do is to avoid acts that can cause kidney injury; adopt healthy lifestyles.

Healthy Lifestyle includes:

• Eliminate tobacco; reduce alcohol intake
• Eliminate meat, dairy products and high-protein diets.

In A prospective study of dietary Meat intake and Risk of incident chronic kidney disease (Parvin Mirmiran et al. J Ren Nutr. 2020 Mar.). The study concluded that higher consumption of total red meat and processed meat was associated with increased risk of incident chronic kidney disease (CKD). The substitution of total red meat and processed meat in the diet with other sources of dietary protein was associated with lower CKD risk.

• Eat plant food products more often. Plant phytochemicals have both antioxidant and anti-inflammatory components.
• Avoid medications like the NSAIDs and chemicals (alcohol, nicotine, etc.,) that could damage kidneys.
• Avoid inactivity. Stay active and remain well- hydrated, always.

Summary

Since there is no specific treatment for AMKD, we must adopt measures that always protect our kidneys from injuries: consume mainly plant-based minimally processed foods, avoid medications and chemicals like alcohol, nicotine that can potentially cause kidney injury. Stay well-hydrated and always stay active.