Natural Substance Produced by Kidneys Prevents UTIs

September 18, 2014

A urinary tract infection confined to the bladder is usually just irritating, but an infection that spreads to the kidney can cause permanent organ damage and even death due to sepsis.

Now a  study from P&S shows that the kidney can sense infections in the bladder and protect itself from bladder infections by flooding the bladder with an antibacterial protein.

The finding helps explain why some people are more prone to urinary tract infections (UTIs) and may lead to new ways to fight the infections, says the study’s senior investigator Jonathan Barasch, MD, PhD, professor of medicine and of pathology & cell biology.

Though it is well known that the kidney continually releases antimicrobial substances that help prevent the growth of bacteria in the urinary tract, less is known about how the kidney responds after an infection takes hold.

A clue came from earlier work by Dr. Barasch, Neal Paragas, PhD, instructor in medical sciences at CUMC; Kai Schmidt-Ott of Max-Delbruck Center for Molecular Medicine; and Kyoshi Mori of Kyoto University. They found that the kidney releases a protein called NGAL when it is injured. NGAL’s ability to prevent bacterial growth raised the possibility that the protein also has a role in the urinary system. An additional clue came from patients admitted to the hospital: NGAL in urine from patients with UTI infections was 10 times higher than in urine from uninfected patients.

In the current study, conducted in mice, Drs. Barasch and Paragas, and Adam Ratner, MD, associate professor of pediatrics at P&S, found that NGAL is an effective antimicrobial in urine and is required to clear a bladder infection.

Ultimately the researchers traced the production of NGAL to the kidney’s intercalated cells, which are known to acidify the urine [from research conducted years before by Qais Al-Awqati, MD, professor of physiology & cellular biophysics and of medicine].

The kidney cells release NGAL when bacteria invade the kidney or when the cells detect bacteria in the bladder through a still-unknown mechanism.

“To me, this means that a bladder infection is a more significant problem than we’ve previously recognized, because there is a systemic effect,” Dr. Barasch says. “Even when bacteria have yet to reach the kidney, the kidney responds, suggesting that there is a continuum between cystitis (bladder infection) and pyelonephritis (kidney infection), diseases that were thought to be distinct.

“Not only NGAL, but also a host of cytokines typical of pyelonephritis were expressed in models of cystitis without overt bacterial infection of the kidney,” Dr. Barasch adds. “The data also broadens our conception of intercalated cells, including them in the family of innate host defenses.”

For physicians, the findings may be important for the treatment of people with distal tubule renal acidosis, who get recurrent UTIs and kidney stones. The disease damages the kidney’s intercalated cells, which leads to basic urine, a condition that promotes stone formation and infection.

“Before it was thought that the kidney stones raised the risk of UTIs,” Dr. Barasch says. But the current work shows that damaged intercalated cells may trigger both components of these urological diseases—both alkaline urine and infection at the same time.


The paper, titled α-Intercalated cells defend the urinary system from bacterial infection, was published July 2014 in The Journal of Clinical Investigation.