Originating from research at KU, treatment for kidney disease passes crucial test

November 05, 2012

By C.J. Janovy

Jared Grantham, M.D.

A large clinical trial has proven that a drug developed as a result of KU Medical Center research is an effective treatment for polycystic kidney disease (PKD), a leading cause of kidney failure. The results have been published online in the New England Journal of Medicine.

Jared Grantham, M.D., University Distinguished Professor and Director Emeritus of the KU Kidney Institute, is a co-author of the paper. The lead author is Vicente E. Torres, M.D., Ph.D., of the Mayo Clinic. Torres presented the trial results on Nov. 3 at the American Society of Nephrology's annual meeting in San Diego.

In a study conducted over three years at multiple international sites, 1,445 patients with polycystic kidney disease took either a placebo or tolvaptan – a drug that was tested on the basis of decades-long research by KU Medical Center faculty, starting with Grantham in the 1970s.

Now an internationally recognized kidney expert, Grantham discovered that, in the kidneys of people with certain gene mutations, a normally helpful antidiuretic hormone caused kidney cysts to secrete and accumulate fluid. The cysts grow and multiply slowly over time – patients in their 20s might have few symptoms, but by the time they are into their 40s or 50s, normally fist-sized kidneys containing these fluid-filled sacs can grow to the size of a football, causing pain and destroying kidney function.

The NEJM study reports that tolvaptan slows the enlargement of cystic kidneys while also slowing the loss of kidney function. Patients who took the drug saw their kidneys grow at about half the rate of the control group over three years. The rate of declining kidney function was also about half, compared to patients taking the placebo.

"This is a significant breakthrough – the first targeted therapy that has been found to effectively slow kidney growth and declining function in PKD in a controlled clinical trial," Grantham says.

In addition to trials at 129 other locations, approximately 15 patients participated at KU, monitored by Franz Winklhofer, M.D. Grantham also notes that KU Medical Center faculty members Vincent Gattone, Ph.D. (now at Indiana University), Darren Wallace, Ph.D., James Calvet, Ph.D., Robin Maser Ph.D, and Professor Emeritus Lawrence Sullivan, Ph.D., all played key roles in advancing the research over the last 30 years.

For Grantham, the scientific quest dates back to the 1940s and his hometown of Johnson, Kan., where he noticed blood in the urine of a high-school football teammate whose grandmother had died of kidney cysts. "It has been a slow process to finally get to the point where we can say we have a treatment for PKD," Grantham says. "Not a cure, but a treatment that promises to slow disease progression."

Dr. Grantham is also the founder of the PKD Foundation, which is celebrating its 30th anniversary. The foundation is a national organization headquartered in Kansas City, Mo., dedicated to promoting research, education, advocacy and awareness to discover treatments and a cure for polycystic kidney disease. The foundation played a key role in developing this treatment by funding and supporting research that made this work possible.

"This is a major milestone for the foundation and the PKD community. The thousands of people who suffer from this devastating disease have been waiting for a treatment such as this for years," says Gary Godsey, PKD Foundation president and CEO. "The foundation is proud to have been a part of this critical work, and our hope is that this is just the first step toward finding other treatments that will improve the quality of people's lives who suffer from PKD."

Last modified: Oct 10, 2013