Researchers identify kidney water-control pathway beyond vasopressin
Mayo Clinic scientists say a probenecid finding may point to ways to reduce the burden of polycystic kidney disease treatment.
By Lucas Ferreira · Science & Environment Writer
3 min read
Mayo Clinic researchers have identified a previously unknown route the kidney uses to conserve water, according to a study published in the Journal of Clinical Investigation. The finding matters because it could help improve treatment for polycystic kidney disease, a genetic condition that can end in kidney failure.
The study was led by Mayo Clinic nephrologist Dr. Fouad Chebib. Mayo Clinic said the work shows that kidney cells can help concentrate urine through a process that does not depend on vasopressin, the hormone long considered central to the body’s water-balance system.
According to Mayo Clinic, the discovery came from experiments with probenecid, an older drug first introduced in the 1940s. Researchers expected the drug to increase cellular activity tied to cyst growth in polycystic kidney disease, but Mayo Clinic said repeated tests showed the opposite result: cyst growth slowed.
A pathway tied to urate
Chebib’s team studied laboratory-grown kidney cell models to examine how cysts form and expand in polycystic kidney disease, according to Mayo Clinic. After the unexpected probenecid results, the researchers looked at how the drug changed the way kidney cells handle urate, a molecule commonly associated with gout.
The study reports that urate can act as a signal inside kidney cells. Mayo Clinic said that signal triggers cellular steps that move water channels to the cell surface, allowing the kidney to take water back into the body and concentrate urine.
That mechanism works apart from vasopressin, according to the Mayo Clinic summary of the study. Chebib said the results show the kidney has another way to preserve water beyond the pathway described in standard physiology models.
Possible effect on PKD treatment
Polycystic kidney disease causes fluid-filled cysts to grow in the kidneys, Mayo Clinic said. The disease can damage kidney function over time, and many patients eventually require dialysis or a transplant.
Mayo Clinic said PKD affects millions of people globally. In the United States, about 140,000 people have autosomal dominant PKD, the most common form of the disorder, according to the institution.
The only approved drug for slowing PKD progression is tolvaptan, according to Mayo Clinic. It works by blocking vasopressin, which can reduce cyst growth, but Mayo Clinic said patients often produce 6 to 7 liters of urine a day while taking it.
That side effect can make treatment hard to tolerate, according to Mayo Clinic. In preclinical work and a small clinical trial, the researchers found that adding probenecid reduced urine volume and nighttime urination while preserving the treatment effect.
Mayo Clinic said patients had an average urine-volume reduction of about 30% after taking probenecid. Many participants went from waking several times a night to urinate to waking about once, and they reported better quality of life, according to the institution.
Next target is new drugs
Mayo Clinic said the researchers do not view probenecid as the likely long-term treatment. The drug is decades old, affects several biological systems and is not widely available today, according to the institution.
The team instead hopes the finding can guide new therapies aimed specifically at the urate-linked water-conservation pathway. Chebib’s interest in kidney disease began after his father was diagnosed with PKD, Mayo Clinic said.
The Journal of Clinical Investigation paper identifies GLUT9b- and ABCG2-mediated urate transport in the collecting duct as part of the vasopressin-independent mechanism of kidney water reabsorption. The study was published in 2026 with the DOI 10.1172/JCI197021.
This story draws on original reporting from ScienceDaily.