Innovative Approaches to Combat Kidney Disease by Targeting Neutrophils

Recent research highlights the potential of new therapies aimed at neutrophils, key white blood cells involved in immune responses, to treat various kidney diseases. When pathogens invade the body, neutrophils rapidly respond by releasing neutrophil extracellular traps (NETs), web-like structures composed of DNA and proteins designed to trap and eliminate harmful microbes. Although NETs are crucial for infection control, their excessive or misplaced formation can cause significant tissue damage, especially within the kidneys.

A comprehensive review published in 'Nature Reviews Nephrology', led by Professor Akihiro Ishizu from Hokkaido University, delves into how dysregulated neutrophil activity and NETs contribute to kidney inflammation and injury. In kidney conditions such as vasculitis, lupus nephritis, thrombotic microangiopathy, diabetic nephropathy, and crystal-related injuries, an overabundance of NETs or impaired clearance mechanisms exacerbate tissue damage.

"Although neutrophils are protective, their overactivation appears to worsen kidney damage," explains Ishizu, the review’s lead author. "This shifting understanding opens avenues for targeted treatments that could minimize side effects compared to traditional immunosuppressants."

Strategies under investigation include blocking the chemical signals like C5a that initiate neutrophil activation, with drugs such as avacopan showing promising clinical trial results. Other approaches focus on inhibiting the enzymes necessary for NET formation, thereby preventing the harmful webs from developing. Additionally, efforts are underway to enhance the breakdown and clearance of NETs using enzymes like DNase I and DNase1L3, although disease-related modifications make this challenging.

The review posits that directly targeting neutrophils and NETs offers a transformative potential for kidney disease treatment. By focusing on specific pathways involved in inflammation and tissue injury, new therapies could reduce reliance on broad-spectrum immunosuppressants, leading to more effective and safer management of kidney health.

"Advancing these targeted therapies can change the landscape of kidney disease management," states Daigo Nakazawa of Hokkaido University, the principal author. "As clinical trials progress, we hope that treatments focusing on neutrophil activity will bestow better outcomes for patients suffering from these chronic and often debilitating conditions."

[Source: https://medicalxpress.com/news/2025-06-kidney-disease-neutrophils.html]