Kidney disease is growing in Africa: Big new study casts light on genetic risk factors

Every minute your kidneys are hard at work, filtering around 200 litres of blood, removing waste, balancing salts and fluids, and regulating blood pressure. This happens without any conscious effort on your part.

But when your kidneys begin to fail, the consequences are devastating, including fatigue, fluid buildup and heart complications. Some people eventually need dialysis or a transplant to stay alive.

Kidney disease is one of the fastest-growing causes of death across the world. Around 850 million people are living with some form of it, more than the combined number of people affected by diabetes and cancer. Chronic kidney disease — when your kidneys slowly lose the ability to do their job — causes approximately 1.5 million deaths each year globally and that toll is rising.

But kidney disease develops silently, with few symptoms until it is already severe.

And the burden is not shared equally. People of African ancestry are four times more likely to develop the most severe form of kidney failure than people of European ancestry. In sub-Saharan Africa, rates of high blood pressure and type 2 diabetes are rising too. Both are leading drivers of kidney damage. Around 30 per cent of adults in sub-Saharan Africa have high blood pressure, and 25 million (one in 20 adults) have diabetes) — mostly undiagnosed and untreated.

Sub-Saharan Africa has lower numbers of kidney specialists, dialysis facilities and transplant services per capita than the rest of the world. Africa as a whole has fewer than one nephrologist per million people. In some African countries there are no kidney specialists at all. The global median is around 10 per million. In high-income countries the figure reaches 23 per million. For most Africans who reach kidney failure, there is simply no treatment available.

Identifying who is at risk before their kidneys fail is therefore vital.

Our recently published research fills a big gap here. We are members of the KidneyGenAfrica consortium, a pan-African partnership that aims to deliver research and training excellence in genomics of kidney disease.

We found new genetic variants that point to kidney disease risk in African populations. And we uncovered differences between the genetic risks faced by people living in Africa, on one hand, and people of African descent living in the North America and Europe, on the other.

This shows how important it is for medicine to be based on relevant research.

Understanding kidney disease

Kidney disease does not appear suddenly. It often develops gradually, shaped by a combination of factors. Some people carry genetic variants, small differences in their DNA, that make their kidneys more susceptible to damage.

Others face environmental risks such as high-salt diets, uncontrolled high blood pressure or diabetes infections. The use of herbal medicines, contaminated water and environmental toxins are risks too.

In most cases, it is the combinations of these factors that determine who gets sick and how quickly. But until recently, African populations had barely featured in the scientific conversation about this. Africa, home to the most genetically diverse human populations on Earth, have been represented in only a small fraction of the world’s genomic research.

That is beginning to change.

Large genetic study of Africans

We analysed genomic data from about 26,000 individuals across eastern, western and southern Africa, and around 81,000 individuals of African ancestry living elsewhere. It’s the largest genetic study of kidney function in continental Africans ever conducted.

Our study sheds new light on the genetics of chronic kidney disease across diverse African populations. It will also support future work aimed at improving prevention, diagnosis and treatment of kidney disease among these populations and worldwide.

The team used a method called a genome-wide association study, which scans the entire human genetic code to find variants linked to a particular trait or disease. Here, the trait of interest was estimated glomerular filtration rate, a standard blood test result that measures how efficiently the kidneys are filtering waste. A lower score signals poorer kidney function and higher risk of disease.

Analysing continental African populations alone, the study identified four relevant locations on genes, including two that hadn’t been reported before.

Adding African-ancestry populations across the diaspora, the number rose to 19 locations, three of them new. Four of these genetic locations were pinpointed with high precision. This means the team was able to identify the specific genetic variant most likely driving the effect, rather than simply flagging a region of the genome where something relevant was happening.

Each newly discovered location is now a potential target for future drugs or diagnostic tools.

The study also examined polygenic scores, which are tools that estimate a person’s overall risk of developing a disease. A key finding here was that scores built using data from genetically similar African populations performed better than scores derived from larger but genetically distant datasets.

This matters enormously for medicine in Africa: the science only works if the reference data matches the population it is meant to serve.

A gene that behaves differently on either side of the Atlantic

An important finding from the study concerns a gene called APOL1. Two variants of the APOL1 gene, known as G1 and G2, increase the risk of several serious forms of kidney disease in African Americans. It was widely assumed that the same risk would apply equally to people living on the African continent.

However, the data suggests otherwise. In continental Africa, these high-risk APOL1 variants occur at lower frequencies (and vary across regions of Africa). Their association with reduced kidney function is markedly weaker than in the African diaspora.

The same gene appears to behave differently depending on where a person lives and what population they descend from.

The finding matters for drug development. Clinical trials for kidney disease treatments must include people living in Africa and not just people of African descent living elsewhere.

What must happen now

Several things must follow from this research if it is to benefit people’s health:

• African health systems must invest in early kidney disease detection. Simple, affordable blood and urine tests can identify kidney damage when lifestyle changes and medication can still make a difference. Genetic risk tools can help identify who needs screening most urgently.

• Pharmaceutical companies must include continental African populations in their clinical trials.

• The global research community must continue investing in African genomic infrastructure — research cohorts and large groups of consenting participants whose genetic and health data are collected and stored for analysis.

This research is evidence that African scientists, working with African communities, can generate knowledge that shifts the global picture. The world’s understanding of one of its most urgent health challenges will be sharper for it.

Segun Fatumo, Professor and Chair of Genomic Diversity, Queen Mary University of London

This article is republished fromThe Conversationunder a Creative Commons license. Read the original article.