- New $2 million grant to advance understanding of polycystic kidney disease and its genetic mechanisms
OKLAHOMA CITY – Polycystic kidney disease (PKD) is a prevalent genetic disorder that leads to the formation of cysts on the kidneys, impacting approximately 500,000 individuals in the United States. It is estimated that one in every 1,000 people will develop some form of cystic kidney disease during their lifetime, with nearly 40,000 residents in Oklahoma affected by chronic kidney disease, according to local health authorities.
For many of these patients, dialysis remains one of the few viable treatment options, with a significant financial burden. Recent research highlights that the average annual cost of dialysis in the U.S. is estimated to be around $40,000.
In response, researchers at the University of Oklahoma are embarking on groundbreaking studies to decode the genetic complexities of PKD, paving the way for innovative treatment options.
Experts have established a connection between PKD and kidney cysts, fibrosis, and a gradual decline in renal functionality, which is crucial for waste and fluid elimination from the body. However, the specific mechanisms contributing to the drop in renal function remain largely unexplored.
“Mutations in certain genes can lead to kidney cysts, altering the organ’s tubular structure,” explained a lead investigator in the study. “What remains unclear is the exact transition from a healthy kidney to a cystic one.”
Since late 2024, a team of researchers at OU Health Sciences has initiated a study backed by a four-year, $2 million grant from a national health institute. Their primary goal is to pinpoint the genes and proteins involved in PKD and assess their impact on renal function.
“Currently, we are aware of approximately 40 genes linked to polycystic kidney disease. However, these genes do not fully clarify the catalyst that transitions normal tubules into dysfunctional cystic structures,” the investigator added.
To shed light on these issues, the research team is focusing on a gene known as Fbxw7, which plays a critical role in cellular functions and may be connected to cyst formation and cellular degeneration. This aspect of PKD has not been previously studied.
Initial experiments indicate that deleting the Fbxw7 gene in a specially designed mouse model may replicate cyst formation associated with PKD. Preliminary results have shown promise.
“Our findings reveal that mice with the Fbxw7 deletion develop a form of slowly progressing cystic kidney disease without typical kidney enlargement or severe fibrosis, mirroring distinct features found in various PKD types,” the research lead stated. Notably, this includes nephronophthisis, a genetic disorder affecting one in 50,000 children globally.
Further investigations into the genetically modified mice demonstrated that declines in renal function corresponded with an abnormal accumulation of the protein SOX9. Remarkably, reducing SOX9 levels by deleting one gene copy successfully restored renal function.
These findings mark a pivotal advancement in recognizing the genes that directly influence fibrocystic kidney diseases and are crucial for identifying potential therapeutic targets for genetic cystic disorders. Future research will focus on cataloging the development of cystogenesis and its modulation by fibrosis, ultimately enhancing understanding of how these processes affect kidney function.
“Gaining insights into these mechanisms will inspire new strategies for addressing cystic kidney disease and improving patient outcomes,” the lead researcher noted.
