Females recover faster from kidney disease, and we're not sure why

Testosterone is to blame for it.
Mert Erdemir
Woman sitting on a bed
Woman sitting on a bed

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Kidney disease or chronic kidney disease (CKD) leads to more deaths than breast or prostate cancers and affects around 37 million people in the U.S., according to kidney.org.

A new study conducted by Duke Health researchers suggests that females hold a molecular advantage that protects them from a kind of cell death that emerges in injured kidneys, according to a press release.

“Kidney disease afflicts more than 850 million people worldwide every year, so it’s important to understand why female kidneys are more protected from these acute and chronic injuries,” said Tomokazu Souma, M.D., Ph.D., assistant professor in the Department of Medicine at Duke University School of Medicine.

“Our study is a step toward identifying the causes and suggests that this female resilience could be therapeutically harnessed to improve kidney repair in both sexes.”

A new potential for boosting the kidney resilience

In their study, the research team employed mice to analyze a recently discovered type of cell death called ferroptosis. It is also known that this type of cell death is dependent on oxidative stress and iron, and it plays a significant role in kidney disorders.

The researchers, who used genetic and single-cell RNA transcriptomic analyses in mice, discovered that compared to males, females have notable protection against ferroptosis through a particular pathway known as nuclear factor erythroid 2-related factor 2, or NRF2.

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NRF2, which keeps cell death in control, is highly active in females, while testosterone reduces its activity in males, triggering ferroptosis and damaging cell resiliency in kidney injury. Further research also revealed that if chemically activated, NRF2 can protect male kidney cells from ferroptosis as well. This is promising for determining NRF2 as a potential therapeutic target to prevent failed renal repair after acute kidney injury.

“By identifying the mechanism in which the female hormonal environment protects and the male hormonal environment aggravates acute and chronic kidney injuries, we believe there is strong potential to boost the resilience of kidneys,” Souma said.

The study was published in the journal Cell Reports.

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