Kidney Disease Is Tougher on Men Than Women, But Why?

Women tend to be better able than men to recover from kidney injury, but why?

Apparently, women have an advantage at the molecular level that protects them from a form of cell death that occurs in injured kidneys, a new study in mice has discovered.

"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 study author Dr. Tomokazu Souma. He is an assistant professor in the department of medicine at Duke University School of Medicine, in Durham, N.C.

"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," Souma said in a Duke Health news release.

In the study, researchers looked at a form of cell death called ferroptosis, which is dependent on iron and oxidative stress, and has been identified as a key player in kidney diseases.

The researchers used a special type of RNA analysis on mice. They found that being female conferred striking protection against ferroptosis through a particular pathway called nuclear factor erythroid 2–related factor 2 (NRF2).

This NRF2 is highly active in females. In males, the sex hormone testosterone reduces NRF2 activity and that promotes ferroptosis and undermines cell resiliency in kidney injury.

The team did additional experiments, finding that chemically activating NRF2 protected male kidney cells from ferroptosis. That means NRF2 could be a potential treatment target to promote 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.

What is acute kidney injury (AKI)?

Acute kidney injury (AKI) is a sudden decline in the ability of your kidneys to work and perform their normal functions. It is often referred to as acute kidney failure or acute renal failure and can lead to chronic kidney disease.

If you are sick and in the hospital, you have a higher chance of developing AKI.

You also have a higher chance of AKI if you:

Just had bypass (or other major) surgery
Were in the hospital for COVID-19 (coronavirus)
Are age 65 or older
Have heart disease, congestive heart failure or COPD (chronic obstructive pulmonary disease)
Have a history of kidney disease
Have severe, uncontrolled high blood pressure
Take insulin for diabetes
Have peripheral artery disease (a condition that makes it hard for your blood to get to your arms and legs)
Are severely dehydrated or unable to keep fluids in your body

AKI is very serious and needs to be treated right away to prevent lasting kidney damage. Therefore, if you notice the following symptoms, it is important to contact your doctor as soon as possible: