UTIs Run Rampant, But Kidney Keeps Its Cool—Here’s The Scoop

Infections in the lower urinary tract rarely migrate to the kidneys. The precise mechanism the human body employs to keep the twin organs disease-free has remained a medical mystery—until now.

Dr. Andrew P. Stewart and colleagues from Cambridge University in England found that highly specialized biological structures called neutrophil extracellular traps—NETs—are pivotal in protecting the kidneys from infection.

NETs are sticky webs of wispy strands that quite literally serve as traps. They prevent bacteria that attempt to migrate northward to the kidneys from the lower urinary tract. NETs add to an array of antimicrobial activities mounted by the body to beat back infection.

In Science Translational Medicine, Stewart and his team presented compelling evidence that sticky mesh-like immune NETs are a crucial antibacterial defense against infection. The team's study revealed the presence of NETs in the urinary tract

These findings highlight the role of NETosis in preventing ascending infections in the urinary tract," Stewart, the study's lead author, wrote

 NETosis is the formation of NETs, which prevent species of bacteria—E. coli, Enterococcal faecalis, Proteus mirabilis, among others—from migrating upward from the bladder to the kidneys. The study focused on E. coli, the most common bacterial cause of UTIs.

The process of NETosis is another wonder of human biology. It reveals how the body and immune system create structures to trap pathogens. The key entity in NETosis is the neutrophil, an immune cell, signaled to undergo a unique form of cell death.

As it succumbs, the neutrophil releases its DNA, histones, and granule proteins, leaving behind a mesh-like structure, a net. E. coli and other bacteria are trapped like insects in a spider's web. NETosis isn't rare because NETs are found in the urine of healthy people.

To get a mental image of a NET, picture a spider's web—not the lacy geometric kind ornamented with dew drops, but the thicker, more heavily woven type found in attics. NETs are created from neutrophils, critically important cells of the immune system. The main difference between a spider's web and a NET is scale. The arachnids' webs are large and visible to the naked eye; a NET is microscopic.

The NETs stop UTIs from spreading and wreaking havoc elsewhere in the urinary tract.

Indeed, bacterial invasion of the lower urinary tract is common, according to the World Health Organization, which estimates that hundreds of millions of people are impacted globally each year. Usually, UTIs are limited to the bladder on rare occasions, the invading microbes defy the body's immunological defenses by migrating up the urinary tract and into one or both the kidneys.

Once infected, the kidneys are susceptible to serious complications. The body has antimicrobial strategies, NETosis helps confine bacteria to the bladder, keeping the kidneys infection-free.

"Lower UTI is common but is rarely complicated by pyelonephritis," Stewart added. Pyelonephritis refers to an infection in one or both kidneys. The condition, which is marked by pain and potent inflammation, requires immediate medical care, doctors say because, in some instances, pyelonephritis can be life-threatening.

The Cambridge team analyzed urine samples from 15 healthy people. The scientists found that one biological entity stood out—the presence of NETs. These structures interacted with a protein called uromodulin, which aided in the formation of large webs that entrapped disease-causing bacteria.

The authors validated these findings in mouse models of UTI caused by E. coli. Stewart and colleagues found that interrupting NET formation allowed bacteria to invade the kidneys.

"We identified neutrophil extracellular traps in healthy human urine that provide an antibacterial defense strategy within the urinary tract," Stewart asserted.

Additionally, the Cambridge experiments showed that leukocyte esterase dipstick tests—one of the most common for UTI detection—work by highlighting neutrophils. It was long assumed that the test detected the overall neutrophil count. Stewart and collaborators found that it pinpointed neutrophils that had released NETs.

Reference:

1. 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

(Input from various sources)

(Rehash/Dr Swati Sharma/MSM)