From Health News Digest
Launch Human Clinical Trial to Halt Progression of Polycystic Kidney Disease
INDIANAPOLIS -- A treatment for a disease that can make kidneys grow as large as footballs before renal failure occurs is the focus of human clinical trials that begin this fall under the guidance of a team of Indiana University researchers and a colleague at the Mayo Clinic.
Under a three-year, $600,000 Food and Drug Administration grant, Bonnie Blazer-Yost and Dr. Sharon Moe will serve as co-principal investigators into whether pioglitazone -- also known by its trade name Actos -- is an effective long-term therapy to stop autosomal dominant polycystic kidney disease, or PKD, in its tracks.
Between one in 400 and one in 1,000 people suffer from PKD, according to the National Institute of Diabetes and Digestive and Kidney Diseases. It accounts for 2.2 percent of kidney failures reported in the U.S. annually, according to the U.S. Renal Data System.
While healthy adult kidneys are the size of a fist and weigh less than a pound, polycystic kidneys can weigh as much as 20 to 30 pounds. The fluid-filled cysts initially grow out of nephrons -- tiny filtering units within the kidney -- but eventually separate from the nephrons and continue their growth while the kidney enlarges as well. Other PKD complications can include high blood pressure, liver cysts and blood vessel problems in the brain and heart.
Autosomal dominant PKD is the most commonly inherited kidney disorder. Children of a parent with the gene mutation have a 50 percent chance of inheriting it. Most cases are identified in patients between ages 30 and 50, and more than half experience kidney failure by age 70.
"It does not seem to affect most people until mid-life. But when it does it becomes painful and increasingly debilitating," Blazer-Yost said. "At present, there are no FDA-approved drugs to treat PKD, and the only therapies are to either aspirate the larger cysts to relieve the pain or perform a transplant once the kidney fails.
"What we hope to demonstrate is the ability to halt or greatly inhibit cystic growth in our trial participants. If this proves successful, it will lead to larger trials with the ultimate goal of having a treatment for PKD that can be used as a lifelong medication."
Blazer-Yost is a biology professor at Indiana University-Purdue University Indianapolis, while Moe serves as a professor and chief of nephrology at the Indiana University School of Medicine. Dr. Robert Bacallao, an associate professor of medicine and director of the Polycystic Kidney Disease Clinic at the IU School of Medicine, also will serve as a co-investigator. Dr. Vicente Torres, a professor of medicine at the Mayo Clinic's Division of Nephrology and Hypertension in Rochester, Minn., will consult and provide magnetic resonance imaging interpretation for the study.
Supplementary funding is provided by the Kansas City, Mo.-based PKD Foundation, which will purchase drugs for the trial. The Indiana University Research and Technology Corp. also is working with Blazer-Yost to find commercial partners for additional drug development.
"This trial demonstrates the strength that Indiana University brings to discovering life-changing treatments for patients when scientists and physicians collaborate," said David Wilhite, IURTC's assistant director of technology commercialization.
Blazer-Yost's work to battle PKD originated in diabetes research. Shortly after arriving at IUPUI in 1993, she worked with GlaxoSmithKline to determine why rosiglitazone, a Type 2 diabetes drug also known as Avandia, caused fluid retention. Her findings revealed that the drug affected a different electrolyte channel -- one involving chloride -- than the drug company expected.
"As it turned out, this was the same chloride channel involved in cyst growth in PKD," Blazer-Yost said. "In PKD, the chloride channel causes chloride secretion into the cysts, water follows and the cysts enlarge."
From there, Blazer-Yost and the late Dr. Vincent Gattone, an IU School of Medicine professor of anatomy and cell biology who died of cancer in 2014, used animal models to study how rosiglitazone and the similar compound pioglitazone may be useful in treating PKD. Through studies funded by IUPUI and the IU School of Medicine, it was shown that both drugs not only delayed PKD cyst growth in rats, but did so in concentrations 10 times smaller than doses used to treat diabetes.
"This is exciting because it diminishes any side effect of these already safe compounds," Blazer-Yost said. "Because of this, we foresee these drugs as being a lifelong medication that will keep the disease from getting worse."
Because pioglitazone already is used to treat diabetes, research could move quickly into human clinical trials, to be based at the IU School of Medicine, Blazer-Yost said. Patient recruitment begins this month, with 28 subjects envisioned for the study's first two phases. For information about volunteering for the trial, contact Kristen Ponsler-Sipes at 317-944-7580, or kmponsle@iu.edu.
Researchers at Charité -- Universitätsmedizin Berlin have developed a biophysical treatment method that allows up to 50 percent more toxins to be removed from the blood of dialysis patients. Use of this technology may result in patients with kidney disease seeing a considerable reduction in the length of dialysis sessions. An initial patent application for this technology was filed in 2011. Now, an international medical technology manufacturer has paid a seven-figure sum to secure ownership of the relevant know-how.
Originally developed at Charité, this innovative method breaks new ground in the area of dialysis technology. It utilizes the effect of alternating current fields to remove toxic substances from the blood. Many substances that are produced naturally in the body during the course of normal metabolism become toxic, particularly once their levels in the blood increase. In persons whose kidneys are diseased, and no longer capable of filtering out toxic substances, these levels will continue to increase and, without intervention, that person will die. Until such a time as an affected patient can undergo a kidney transplant, the only option is to undergo regular dialysis.
A proportion of the toxins that need to be eliminated bind to proteins. However, conventional dialysis techniques have so far been unable to filter out toxins in protein-bound form. "After a long period of development, we have achieved a promising breakthrough," says Prof. Dr. Walter Zidek, Head of Charité's Department of Nephrology and Endocrinology, adding that "this new technology makes it possible to separate toxic substances from proteins. It achieves this by guiding them through an alternate current field of a specific frequency and strength." Prof. Zidek goes on to explain that "once the connection between toxins and proteins has been broken, the toxins can be removed from the patient's blood using conventional dialysis technology, and the patient's overall burden of toxins reduced."
Since first being patented by Charité, the underlying process has undergone further and intensive development, and the technology has now been sold to a large, international medical technology manufacturer. The new technology has considerable potential for application within the health care industry of the future. Not only does it promise a reduction in dialysis time, in addition to an increase in patient quality of life, it also promises to lead to improved survival times in patients waiting to undergo a kidney transplant. In conjunction with German developers, Prof. Zidek's team at Charité will continue to test and develop the technology, with the aim of transferring it to clinical practice. A clinical trial in patients is scheduled for next year, and constitutes the final testing stage.
PKD Foundation News
From PKD Foundation
PKD Foundation staff and advocates visit Capitol Hill
Originally developed at Charité, this innovative method breaks new ground in the area of dialysis technology. It utilizes the effect of alternating current fields to remove toxic substances from the blood. Many substances that are produced naturally in the body during the course of normal metabolism become toxic, particularly once their levels in the blood increase. In persons whose kidneys are diseased, and no longer capable of filtering out toxic substances, these levels will continue to increase and, without intervention, that person will die. Until such a time as an affected patient can undergo a kidney transplant, the only option is to undergo regular dialysis.
A proportion of the toxins that need to be eliminated bind to proteins. However, conventional dialysis techniques have so far been unable to filter out toxins in protein-bound form. "After a long period of development, we have achieved a promising breakthrough," says Prof. Dr. Walter Zidek, Head of Charité's Department of Nephrology and Endocrinology, adding that "this new technology makes it possible to separate toxic substances from proteins. It achieves this by guiding them through an alternate current field of a specific frequency and strength." Prof. Zidek goes on to explain that "once the connection between toxins and proteins has been broken, the toxins can be removed from the patient's blood using conventional dialysis technology, and the patient's overall burden of toxins reduced."
Since first being patented by Charité, the underlying process has undergone further and intensive development, and the technology has now been sold to a large, international medical technology manufacturer. The new technology has considerable potential for application within the health care industry of the future. Not only does it promise a reduction in dialysis time, in addition to an increase in patient quality of life, it also promises to lead to improved survival times in patients waiting to undergo a kidney transplant. In conjunction with German developers, Prof. Zidek's team at Charité will continue to test and develop the technology, with the aim of transferring it to clinical practice. A clinical trial in patients is scheduled for next year, and constitutes the final testing stage.
PKD Foundation News
From PKD Foundation
PKD Foundation staff and advocates visit Capitol Hill
PKD Foundation staff and advocates spent two days on Capitol Hill, meeting with elected officials about how they can help fight PKD. Here is a summary of the trip:
On Sept. 9, we were fortunate to have productive and informative discussions on the 21st Century Cures bill (H.R. 6) and other issues of specific interest to PKD patients and their families with Reps. Fred Upton (R-MI) and Diana DeGette (D-CO), the prime authors of the bill.
We also met with Rep. Emanuel Cleaver (D-MO), who represents the PKD Foundation's hometown of Kansas City, MO. He gave us a lot of his time and offered to help the PKD Foundation with its future efforts.
Most of our Sept. 9 meetings occurred on the Senate side of Capitol Hill. Sen. Tammy Baldwin (D-WI), a member of both the HELP and Appropriations Committees, gave us a few minutes before going to an important debate on the Senate Floor.
We discussed patient safety with the health policy aide to Sen. Dick Durbin (D-IL), the Senate Democratic Whip. The Senator is concerned about patient safety. We discussed S. 289, his American Cures Act, which would increase funding for biomedical research at the NIH and elsewhere by five percent.
The rest of our meetings were spent with the key health policy advisors of a number of key Health, Education, Labor & Pensions Committee (HELP) Committee Senators: Sen. Patty Murray (D-WA), the top Democrat on both the HELP Committee and the Labor/HHS Appropriations Subcommittee; Sen. Pat Roberts (R-KS), a HELP member; Sen. Tammy Baldwin (D-WI), who serves on both HELP and the Senate Agriculture Appropriations Subcommittee that funds the FDA.
Some of the health aides mentioned the FDA's current accelerated approval process and did not understand why the 21st Century Cures bill was needed. We tried to address their concerns during the meeting and will provide additional information in the future.
Several aides mentioned that a draft Senate bill, written by HELP Chairman Lamar Alexander (R-TN) and Sen. Murray, should be released by the end of September. They will ask stakeholders for their comments, and we certainly will provide input, especially on the importance of retaining HR 6's biomarker and surrogate endpoint language.
One of our final meetings occurred with the health policy advisor to Sen. Ben Cardin (D-MD), who serves on the Finance Committee that oversees Medicare. The Committee is working on a Medicare bill that could change the prescription drug program (Part D). We will provide Sen. Cardin with information on whether improvements in Part D would help kidney patients that use up their current immunosuppressant drug coverage.
PKD advocates may want to contact these elected officials, if any of them represent you. You should thank them for meeting with the PKD Foundation and encourage them to support the strongest possible 21st Century Cures bill this year.
On Sept. 10, the PKD Foundation participated in the annual Kidney Community Advocacy Day in Washington, D.C. Advocates representing 16 patient and health professions spent the day urging Congress to provide more funding for kidney disease research and to pass a bill to promote organ donation.
In total, more than 90 advocates from 16 organizations met with 110 congressional offices, including with 14 Senators and Representatives. Together, Kidney Community Advocacy Day participants raised the profile of kidney disease, made the case for investing in kidney research, and built support and excitement for the forthcoming Living Donor Act.
Sharing Life
From Columbia Daily Tribune, Columbia, Missouri, By CAROLINE DOHACK
Members of Peggi Moore’s family share a lot.She and her three siblings — Patty Klein, 62; Linda Cheatham, 67; and Craig Klein, 59 — as well as their mother, Annamae Evers, have polycystic kidney disease, or PKD, a genetic disorder characterized by the growth of cysts on the kidneys.
According to the PKD Foundation, cysts can be as tiny as pinheads or as large as grapefruits. So, some people can go their lives without knowing they have the disease, while others are greatly affected.
A healthy kidney is about the size of a clenched fist. With advanced PKD, a kidney can grow to the size of a football. As the kidneys grow larger, they lose function. Because the kidney’s job is to filter blood to remove waste and excess fluid, when their function is compromised, toxicity builds up. When this happens, the person with PKD has two treatment options: dialysis or kidney transplant.
Moore, her siblings and their mother all have had life-saving kidney transplants.
“We just like doing things together,” joked Moore, 63.
Last Saturday, the family — along with their family, friends and living donors — got together at the clubhouse at Cambridge Place for a Hawaiian luau-themed Gift of Life celebration.
For Moore and her family, this celebration was possible because of those who donated kidneys. On average, a patient needing a kidney transplant will spend three to five years waiting. That is, unless he or she can find someone willing to do a living donation or, as Moore puts it, BYOD — bring your own donation.
Cheatham, who celebrated the 25th anniversary of her transplant on Aug. 9, found her match in family friend Robin Ward.
The first step in becoming a donor was a blood typing test to see if Cheatham and Ward were compatible. Ward is type O, making her one of the so-called universal donors. The next step was for Cheatham to receive a mini-transfusion of Ward’s blood to see if her body would accept it.
Ward also underwent a host of other tests to see if there were any undiagnosed diseases lurking.
Additionally, Ward had to meet with a psychologist. At the time, living donors were a rare concept, and so the physicians wanted to ensure that her motives were altruistic — meaning she wasn’t being paid or coerced into relinquishing an organ.
After Cheatham and Ward had satisfied all the requirements, the only thing they had to do was agree on a date for the surgery.
“If you’re BYOD, it can be as soon as they can schedule it,” Cheatham said.
For her part, Ward said there was no reason not to donate a kidney to her friend. She never worried that she wouldn’t live without one of her kidneys; her grandmother had been born with only one kidney, and she had lived until her 80s.
What’s more, Ward had no children. To donate a kidney to Cheatham was a way to have a living legacy.
“It was probably the most selfish decision I ever made,” Ward said. “I could do something good while still being here.”
After the transplant, during which Ward’s kidney was implanted into Cheatham’s pelvic cradle, both donor and recipient were back to their normal lives within a relatively short period of time.
“The doctors told me we couldn’t sky-dive or play tackle football for a year,” Cheatham said.
“But in six months, I was skiing and she was scuba diving,” Ward said.
It was a significantly improved quality of life from what Cheatham experienced before the transplant.
“I felt like crud. I had a loss of appetite. I itched all over,” Cheatham said.
Patty Klein recalls feeling fatigued — to the point that she often had to leave work early — before her transplant.
“I didn’t want to talk to people. On the weekends, if I got my laundry done, I was lucky,” Klein said.
A year after Cheatham’s transplant, Evers received a kidney from a deceased donor. This was after 10 years of dialysis treatments.
“One dialysis treatment is too many,” Moore said.
Patty Klein then received a kidney from a deceased donor in 1995, and Craig Klein received a kidney from his father-in-law, Dave Babel, in 2000. Moore received one from a living donor in 2002 and then another in 2009. [Read more]
Seeking Kidney
From WSB-TV, Channel 2, Atlanta, Georgia
A Clayton County man is in desperate need of a new kidney after he contracted the West Nile Virus following his first kidney transplant.
“I need someone, basically a miracle,” Randy Daniel, 59, told Channel 2’s Craig Lucie.
Daniel was born with polycystic kidney disease, also known as PKD, which causes clusters of cysts to develop in a person's kidneys.
In March 2003 a family member gave him a new kidney.
“It was from a very dear cousin of mine, Donna Oaks,” he said. “I received the transplant and was one of the happiest people.”
But when Daniel walked outside one day, things nearly took a deadly turn.
Daniel was working on his trailer in his backyard not long after his first transplant when he felt a mosquito bite him on his right cheek.
“The welt from the mosquito bite was very large. It left a golf ball-sized bump on my cheek,” he said.
With that one bite, Daniel contracted West Nile virus.
“He was in the hospital in a coma for 12 days. After that point, it caused a lot of damage to the kidney and unfortunately in 2007 that kidney failed,” said his wife.
Now Daniel is in need of a new transplant and prays every day for someone to come forward and be a match.
“I need a living donor. Someone to come forward with a good healthy kidney that would be placed in my body that would truly give me life back,” he said.
Daniel said they don't have any leads so far.
Daniel, who is blood type O+, is on the transplant list at Piedmont Hospital. See his Facebook page here for more information.
He said even if you are not a match for him, you may be a match for someone else and that's what he and his wife would love to see.
Daniel has been featured, along with hundreds of others in need of a kidney, on the Facebook page Callaway’s Angels, which was started last year by the wife of a Greensboro police officer who received a kidney through a social media campaign.
“Help us find a kidney — kidney coordinator Kathryn O’Dea 720-754-2164.”
That’s the Facebook page that is promoting the desperate search for a kidney for Bob Ellis, 59, a Holyoke High School graduate who now lives north of Ovid, near Chappell, Neb.
Ellis has known most of his life that he has a hereditary condition called Polycystic Kidney Disease. His grandfather had it, his dad did and his younger brother, Rod, had a kidney transplant six years ago as a result of PKD.
In fact, Ellis’ own son and at least one of his two daughters have tested positive for the hereditary disease.
As a young kid, Ellis said he was diagnosed with PKD. He said his mom, Bonnie McFadden of Holyoke, told him he had a good-sized cyst at that time and doctors said he wouldn’t live past a certain age.
He said he didn’t really worry about it. He grew up on the ranch, team roped, rode bulls and played football. He knew eventually it would get him.
Younger brother Rod had a high school classmate donate a kidney for a transplant six years ago, and Rod has continued to urge his brother to start the search.
Bob said he has been in a study at the University of Colorado for a number of years, so he was watching his situation. However, it has started getting worse.
Now, one month ago, his doctor indicated Ellis is two to six months away from going on dialysis, and his kidneys are functioning at 11 percent.
Ellis said he was put on a potassium blocker and taken off his blood pressure pill because it creates creatine. However, he started swelling up, so that had to be adjusted.
Right now, he said he just gets tired, and it’s getting very urgent to find a kidney donor.
Ellis is on the National Kidney
Transplant list, but the waiting period for getting a kidney can be three years or more.
Rod Ellis began his search for a living kidney donor in November of 2008, after having been diagnosed with PKD in early 2002.
His success story through the generosity of his high school friend and classmate Clay Warren has prompted him to help get the word out about his brother’s escalating kidney failure.
People are usually born with two kidneys but can function normally with only one.
Bob said if a person donates a kidney and then something happens to their own, they will automatically go to the top of the kidney transplant list.
To be a living donor, one must be between the ages of 18-60, and the blood type must be compatible with Ellis’.
A donor needs to be in good health and free of high blood pressure, diabetes, kidney disease or cancer. A complete medical history and physical examination will need to be completed.
Further information can be provided by kidney coordinator Kathryn O’Dea at 720-754-2164. Ellis would be glad to share more information and can be contacted at 970-948-7773.
