When harmful bacteria or other microorganisms enter the body, neutrophils—a type of white blood cell—are among the first to respond. They release strong defenses to trap and kill these threats. One key defense is called neutrophil extracellular traps, or NETs. NETs are web-like structures made from DNA and proteins. They work like sticky nets that catch microbes and stop them from spreading.
However, while NETs help fight infections, scientists have found that they can also cause serious damage if they form in the wrong place or at the wrong time. This is especially a problem in the kidneys. Too many NETs, or failure to clear them away properly, can cause inflammation and damage kidney tissue.
A new review published in the journal Nature Reviews Nephrology explains how neutrophils and NETs affect many kidney diseases. The study was led by Professor Akihiro Ishizu from Hokkaido University’s Faculty of Health Sciences.
If the immune system does not control NETs well, inflammation can harm the kidneys’ delicate blood vessels and filtration systems. This damage can lead to serious conditions such as ANCA-associated vasculitis, lupus nephritis, thrombotic microangiopathy, diabetic kidney disease, and crystal-induced kidney injury.
“Neutrophils usually protect us, but in these diseases, they seem to cause problems,” said Ishizu, the review’s corresponding author.
“We have long known that inflammation is important in kidney disease. Now we see that neutrophils and NETs actively worsen the damage. This opens new possibilities for treatment.”
Researchers are testing several ways to stop neutrophils from causing harm. One method blocks the chemical signals that activate neutrophils. For example, a molecule called C5a promotes inflammation. Drugs like avacopan, which block C5a receptors, have shown good results in clinical trials for vasculitis and may be used more widely soon.
Another approach tries to stop NETs from forming. Scientists are creating drugs that block enzymes and proteins inside neutrophils responsible for making these DNA webs. By preventing NET formation, they hope to stop the inflammation cycle that leads to kidney failure.
There is also research on helping the body remove NETs more effectively. Enzymes such as DNase I and DNase1L3 can break down NETs, but NETs changed by disease can be harder to clear. Figuring out how to solve this is an important research focus.
The review suggests that targeting neutrophils and NETs could change how kidney diseases are treated. Until now, treatment mostly used general immunosuppressive drugs, which can make patients more vulnerable to infections and other risks.
“The exciting part is that by targeting the specific pathways causing NETs and tissue damage, we may provide better treatments with fewer side effects,” said Daigo Nakazawa from Hokkaido University, the review’s first author.
“We hope that as clinical trials progress, therapies targeting neutrophils will help slow or even stop kidney disease.”
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