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Targeting the Uneven Burden of Kidney Disease on Black Americans – The New York Times

May 17, 2022
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Targeting the Uneven Burden of Kidney Disease on Black Americans – The New York Times
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“I was all for it,” Malcolm said. So was Martin.

When they were tested, the brothers learned they had the variants and that the variants, not lupus, most likely were damaging their kidneys. They hardly knew how to react.

“I am still trying to grapple with it,” Malcolm said.

But Dr. Olabisi was not surprised. Researchers think the variants cause kidney disease only when there is a secondary factor. A leading candidate is the body’s own antiviral response, interferon, which is produced in abundance in people with lupus.

High levels of interferon also occur in people with untreated H.I.V. As happens in people with Covid-19, they can suffer an unusual and catastrophic collapse of their kidneys if they have the variants. Other viral infections, including some that may go unnoticed, can elicit surges of interferon that could set off the APOL1 variants. Interferon is also used as a drug to treat some diseases including cancer and was tested as a treatment for Covid patients.

For now, there is little Malcolm and Martin can do except take medications to control their lupus.

Martin said he understands all that, but he’s glad he learned he has the variants. Now, he knows what he might be facing.

“I’m the kind of person who likes to plan,” he said. “It does make a difference.”

From a Gene to Drugs

While Dr. Olabisi is waiting to start his study, a drug company, Vertex, has forged ahead with its own research. But there was no agreement on how APOL1 variants caused kidney disease, so it was not clear what a drug was supposed to block.

“If you don’t understand the mechanism, that means you can’t measure effects in a lab,” said Dr. David Altshuler, chief scientific officer at Vertex. “And if you can’t measure effects in the lab, that means you can’t correct them.”

It was known how the APOL1 protein protected against sleeping sickness — it punched holes in the disease-causing trypanosomes, making them swell with fluid and burst.

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