From the New York Times science section:

Targeting the Uneven Burden of Kidney Disease on Black Americans

New treatments aim for a gene variant causing the illness in people of sub-Saharan African descent. Some experts worry that focus will neglect other factors.

By Gina Kolata
May 17, 2022

… Kidney specialists have long known that Black Americans are disproportionately affected by kidney disease. While Black people make up about 12 percent of the U.S. population, they comprise 35 percent of Americans with kidney failure. Black patients tend to contract kidney disease at younger ages, and damage to their organs often progresses faster.

Social disparities and systemic racism contribute to this burden, but there is also a genetic factor. Many with sub-Saharan ancestry have a copy of a variant of the gene APOL1 inherited from each parent, which puts them at high risk. Researchers have known for a decade that APOL1 is one of the most powerful genes underlying a common human disease.

But there is hope now that much of this suffering can be alleviated. As many as 10 companies are working on drugs to target the APOL1 variants. And Dr. Olabisi has a federal grant to test whether baricitinib, a drug that treats rheumatoid arthritis, can help kidney patients with the variants. …

While it has long been known that kidney failure occurs in African Americans five times as much in as it does in white Americans, “We had never been able to understand all the reasons,” said Dr. Neil Powe, a professor of medicine and an epidemiologist at the University of California, San Francisco.

Researchers began looking for a genetic cause. Finally, a little more than a decade ago, a Havard [sic] team led by Giulio Genovese, Dr. David Friedman and Dr. Martin Pollak found it: variants of APOL1 that ramped up the gene’s activity.

It was a complete surprise. APOL1 is part of the immune system and can destroy trypanosomes — protozoa that can cause illnesses. But no one expected it to have anything to do with the kidneys.

It turns out that the variants rose to a high frequency among people in sub-Saharan Africa because they offer powerful protection against deadly African sleeping sickness, a disease caused by trypanosomes. It is reminiscent of another gene variant that protects against malaria but causes sickle cell disease in those who inherit two copies. That variant became prominent in parts of Africa and other areas of the world where malaria is common, but sickle cell variants are much less common than APOL1 risk variants.

About 39 percent of Black Americans have one copy of the gene’s risk variants; another 13 percent, or nearly 5.5 million, have two copies. Those with two copies are at increased risk for fast progressing kidney disease that often starts in young adulthood. Approximately 15 percent to 20 percent of those with two copies develop kidney disease in their lifetime.

So, sounds like about 2% of African-Americans will develop kidney disease from having two copies of this gene.

In contrast, 7.7 percent of Americans with African ancestry have one copy of the sickle cell variant, and 0.3 percent have two copies.

Full-blown sickle cell anemia caused by inheriting both copies is usually fatal in childhood, so the frequency of how many people get the falciparum malaria–fighting benefits of inheriting one copy of the sickle cell gene is limited by lethal detriments of inheriting two copies. (The chance of getting both copies is more or less the square of the chance of getting one copy.) On the other hand, kidney failure can occur after the reproductive years, so the anti–sleeping sickness variant is less of a Darwinian loser in large percentages.

“What nature gave with one hand, it took away with the other,” Dr. Olabisi said.

One way to treat kidney disease might be using medicines that block the gene and its variants from acting in the body. But researchers had to find out if APOL1 was necessary for kidney function. If it was, drugs that blocked it might do more harm than good.

Researchers found an answer: A farmer in India had no APOL1 gene. His kidneys were totally healthy.

… But ethical issues have tempered some experts’ enthusiasm about the genetic discoveries.

Harriet A. Washington, a lecturer in ethics at Columbia University and author of the book “Medical Apartheid,” worries that knowledge of the role of APOL1 variants can drive the medical establishment toward “a blame-the-victim approach signaling an inherent flaw in African Americans.”

The implication, she said: “This is something happening in nature, so what can we do about it?” Such an attitude, she added, “invites futility and absolves health care from treating sufferers.”

Joseph L. Graves, Jr., a professor of biological sciences at North Carolina Agricultural and Technical State University, raised another issue. “We don’t want to fall into the myth of the genetically sick African,” he said.

“All populations have genetic variants, but the action of those variants is determined by the environment in which those people live,” Dr. Graves explained. “People want to find simple explanations for complex phenomena. Find a genetic variant and make the story simple, but that’s not how it works. Environmental effects are really important.”

He added that for Black Americans, profound environmental effects rise from structural racism — inequitable effects of law and policies — which can lead to a lack of access to health care, including preventive care to ward off chronic illness.

Erika Blacksher, an ethicist at the nonprofit Center for Practical Bioethics in Kansas City, Mo., added that while finding “a treatment that might counteract the effect of the genetic variant is good news,” she worried that social inequities could not be disentangled from the high rate of kidney disease among those with sub-Saharan African ancestry, not all of whom have the APOL1 variant. Emphasizing the variants, she said, “deflects from our social responsibility to actually change the conditions that contribute to the onset of chronic kidney disease.”

The biggest single environmental reason for the high rate of kidney disease in African-Americans is that Africa has numerous places infested with sleeping sickness. But African-Americans don’t live in Africa anymore, so this particular genetic adaptation to the African environment is no longer useful.

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