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Cambridge, UK – A new study from Cambridge University has unraveled a longstanding medical mystery: why kidney infections remain rare despite urinary tract infections (UTIs) being extraordinarily common. The research, published in Science Translational Medicine, reveals that specialized immune structures called neutrophil extracellular traps (NETs) play a critical role in protecting the kidneys from invading pathogens.
The Defense Mechanism Behind NETs
NETs are sticky, web-like structures formed by neutrophils, a type of white blood cell. These microscopic traps ensnare bacteria attempting to travel from the bladder to the kidneys, preventing the spread of infection. This process, known as NETosis, is a key antimicrobial strategy that helps contain bacteria like Escherichia coli (E. coli), the most common cause of UTIs, to the lower urinary tract.
Dr. Andrew P. Stewart, the study’s lead author, highlighted the importance of this discovery. “Our findings show that NETosis is a critical defense against ascending infections in the urinary tract,” Stewart said. “Without it, bacteria can invade the kidneys, leading to serious complications like pyelonephritis.”
Experiments Uncover the Mystery
The Cambridge team used advanced imaging techniques and experiments in both humans and mice to uncover the role of NETs. Urine samples from 15 healthy individuals revealed the presence of NETs, which interacted with a protein called uromodulin to form large, bacteria-trapping webs. In mouse models, disrupting NET formation allowed bacteria to ascend to the kidneys, underscoring their protective role.
Remarkably, the study also shed new light on the mechanics of routine leukocyte esterase dipstick tests, commonly used to detect UTIs. These tests identify the presence of neutrophils, but Stewart’s team found that they specifically detect neutrophils that have undergone NETosis. This revelation revises decades of assumptions about how the dipstick test works.
Implications for UTI Treatment and Diagnosis
UTIs affect hundreds of millions of people globally each year, according to the World Health Organization, with symptoms typically confined to the bladder. However, on rare occasions, bacteria can ascend to the kidneys, causing pyelonephritis—a painful and potentially life-threatening condition. Understanding the role of NETs offers new insights into how the body limits bacterial spread and could pave the way for improved diagnostic and therapeutic approaches.
“These findings not only deepen our understanding of the immune system’s intricacies but also highlight how the body uses its natural defenses to protect vital organs like the kidneys,” Stewart said.
The discovery of NETs in healthy urine and their role in preventing kidney infections marks a significant advancement in medical research, potentially shaping the future of UTI treatment and prevention strategies.
Reference:
Andrew P. Stewart et al., “Neutrophil extracellular traps protect the kidney from ascending infection and are required for a positive leukocyte dipstick test,” Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adh5090
