John Pope, M.D.
Bladder fibrosis research enhanced
John Pope, M.D., has received a $1.2 million grant from the National Institutes of Health (NIH) to investigate ways to make a surgery he regularly performs obsolete.
At the heart of this issue is a condition called bladder fibrosis, a common side effect of the birth defect spina bifida, which occurs in about one in 1,000 births in this country.
Built-up pressure in the bladder of a child with a sphincter that is unable to open on its own causes the bladder muscle to thicken and become fibrotic, or scarred. When a bladder becomes severely fibrotic, it can no longer hold even small amounts of urine, which can backflow into the kidneys and cause kidney failure. Bladder fibrosis, in fact, is the leading cause of kidney failure in children.
Current treatment is a dramatic surgery that takes a section of the bowel and uses it to reform — and expand — the bladder and spare the kidneys.
“But the expansion surgery comes with some serious risks of its own,” explained Pope, associate professor of Urologic Surgery at the Monroe Carell Jr. Children's Hospital at Vanderbilt. “There is an increased risk of bladder cancer, bladder stones and metabolic issues because of re-absorption of waste products by the bowel tissue.”
Pope's research will determine if there might be a way to avoid this surgery altogether by interfering with the biochemical chain of events that leads to fibrosis.
“We got our ideas from cardiology,” Pope said. “If you think about it, the bladder is not unlike the heart, which is also a smooth muscle pump.”
Research in heart disease has discovered that when pressure in the heart leads to thickened and ineffective muscle, a protein called transforming growth factor-beta (TGFbeta) plays a major role in the thickening. Studies in the kidneys have identified the Renin-Angiotensin System (RAS) as a regulator of TGFbeta in the urinary system.
“In a rat model, we will cause a backup in the bladder and then watch what happens to levels of TGFbeta and the RAS,” Pope said. “We'll be examining some of that bladder tissue to see if existing medications, like blood pressure drugs, might be able to interrupt this RAS, TGFbeta cycle effectively. In addition, we will take bladder cells in culture to see if changing TGFbeta levels in those cells will lead to decreased fibrosis.”
Once Pope has his answers, he may very well have set the stage for human trials to discover if, in the future, afflicted children can take a simple pill, or some other form of medication, to either slow, or stop, the thickening of their bladders. If that can be done, surgery can be avoided.