Target the irregular burden of kidney disease on black Americans
“I agreed,” Malcolm said. So what Martino.
When tested, the brothers learned they had the variants and that the variants, not lupus, were most likely damaging their kidneys. They didn’t know how to react.
“I’m still trying to deal with it,” Malcolm said.
But Dr. Olabisi was not surprised. Researchers think variants cause kidney disease only when there is a secondary factor. A leading candidate is the body’s antiviral response, interferon, which is produced in abundance in people with lupus.
High levels of interferon also occur in people with untreated HIV.As it happens in people with Covid-19, they can experience an unusual and catastrophic collapse of their kidneys if they have the variants. Other viral infections, including some that may go unnoticed, can cause interferon spikes that could trigger APOL1 variants. Interferon is also used as a drug to treat certain diseases including cancer and has been tested as a treatment for Covid patients.
For now, there’s little Malcolm and Martin can do other than take medications to control their lupus.
Martin said he understands all of this, but is glad he learned he has the variants. He now he knows what he might be up against.
“I’m the kind of person who likes to plan,” he said. “It makes a difference.”
From a gene to drugs
while Dr. Olabisi is waiting to start his study, a pharmaceutical company, Vertex, has been carrying out its research. But there was no agreement on how the APOL1 variants caused kidney disease, so it wasn’t clear what should block a drug.
“If you don’t understand the mechanism, it means you can’t measure the effects in a laboratory,” said Dr. David Altshuler, scientific director of Vertex. “And if you can’t measure the effects in the lab, it means you can’t correct them.”
The APOL1 protein was known to protect against sleeping sickness: it punctured the trypanosomes that cause disease, causing them to swell with fluid and burst.