Tag Archives: Kidney

UAB – UAB News – $17 million multi-institutional grant to maximize kidney transplant survival

by Tyler Greer

August 04, 2014 Print Email

The University of Alabama at Birmingham is participating in a new seven-year, $17 million multicenter study funded by the National Institutes of Health to determine whether certain immune system cells and/or a drug used for treating rheumatoid arthritis can improve and maintain the long-term health of kidney transplant recipients.

The goal of the study is to reduce or eliminate inflammation in kidney transplants and prevent the associated decline in graft function, thereby maximizing long-term organ survival. It will involve two clinical trials in parallel by researchers at four sites around the country.

Roslyn Mannon, M.D., professor in the School Medicine in the Division of Nephrology and professor of surgery in the Division of Transplantation, is the principal investigator for the grant at UAB. University of California, San Francisco is the lead institution for the study.

Mannon, director of research for the Comprehensive Transplant Institute and immediate past president of the American Society of Transplantation, says the newly funded series of trials to take place at UAB will involve the use of regulatory T cells, or Tregs, and the use of an anti-IL6 receptor antibody. The programs are expected to begin this fall.

“We have been a site for NIH and Clinical Trials in Organ Transplantation studies since 2009,” said Mannon, also a member of the NIH steering committee for the CTOT and a member of the mechanistic studies committee. “In the current funded projects, we collaborate with other institutions on three clinical trials devoted to kidney transplant patients. We have 27 UAB patients enrolled to study a novel combination of immunosuppression with a total of 65 enrolled in all three sites. Additionally, one study is specifically for kidney and pancreas transplant recipients, and is one of the first studies in this patient population to be performed in the past 15 years. To be a part of this new multicenter study is great news. We will continue to participate in these cutting-edge national research efforts.”

Despite advances in transplantation — reducing early acute rejection rates to less than 15 percent and improving one-year graft survival to more than 90 percent — long-term graft success rates have remained unchanged at 4 percent loss annually. A major contributor is the progression of interstitial fibrosis and tubular atrophy in the kidney.

The Comprehensive Transplant Institute provides a means to expand patient options, including incompatible transplantation and kidney-paired donation and new access to transplants for patients with HIV or hepatitis C infection. Every gift will help expand UAB’s expertise in transplant immunology, transplant pathology, and outcomes research, which will have a direct impact on patient care. The cells that the researchers are focused on are Tregs, a small population of lymphocytes that suppress the activity of other immune cells. They maintain normal immune system homeostasis and safeguard against autoimmune diseases, and their immunosuppressive properties also can be harnessed to control transplant rejection.

Tregs have the potential to induce long-term donor-specific tolerance without impeding desired immune responses to pathogens and tumors in transplant patients.

The principal investigator of the study is Flavio Vincenti, M.D., UCSF professor of medicine and a kidney and pancreas transplant specialist at UCSF Medical Center. Other participating institutions are Emory University and Cedars-Sinai Medical Center.

“This grant allows us to work toward achieving two important advances in the transplant field,” said Vincenti. “We can introduce personalized medicine by treating patients based on molecular profiling of their kidney. We also can allow control of the response to the transplant by the patients’ own immune systems by regulatory T cells, either through infusions or pharmacologically.”

Researchers believe inflammation can be controlled in kidney transplant recipients by increasing the number or activity of Tregs, either by infusing them into the body or by blocking interleukin 6 (IL6) with the drug tocilizumab.

To do so, they will conduct two clinical trials — Treg Adaptive therapy in Subclinical inflammation in Kidney transplantation, or TASK, and Therapy to Reduce Allograft Inflammation with IL6 inhibition, called TRAIL.

The trials will involve expert clinical investigators, translational Treg biologists and mechanistic core researchers. The four selected transplant centers are noted for high-quality patient care, high patient volume and the necessary translational infrastructure to ensure successful recruitment. In fact, there already are pre-existing, productive working relationships among the transplant centers and investigators.

Learn more on UAB’s research efforts to help transplanted patients keep their organ permanently and listen to Mannon’s podcast on kidney research at UAB’s The Mix.

via UAB – UAB News – $17 million multi-institutional grant to maximize kidney transplant survival.

Fundraisers set for double kidney transplant recipient – Loveland Reporter-Herald

By Shelley Widhalm

Reporter-Herald Staff Writer

POSTED:   08/02/2014 11:05:05 AM MDT

Jacob Whitler, 16, takes his dog named Buddy for a walk Friday morning near his home in Loveland. Whitler had a kidney transplant a month ago with his mother, Lisa Whitler, as the donor. (Steve Stoner / Loveland Reporter-Herald)

Lisa Whitler talks about the surgeries that she and her 16-year-old son, Jacob, underwent recently when she donated a kidney to Jacob. (Steve Stoner / Loveland Reporter-Herald)

If you go

What: Fundraising event in honor of Jacob Whitler.

When: Thursday, Aug. 7.

Where: Texas Roadhouse, 4633 S. Timberline Road, Fort Collins.

Benefit: 20 percent of sales will be donated, a flier advertising the event is required; go to http://cotaforjacobw.com/node/315.

Other events:

• Sept. 13, Mums sale, preorder perennial flowers and pick them up at the Foundations Church parking lot, 1380 Denver Ave.

• Oct. 19, Bowling tournament, Sweetheart Lanes, 2320 N. Lincoln Ave., Loveland. RSVP by Oct. 5.

To make a donation: Mail it to the Children’s Organ Transplant Association, 2501 W. COTA Drive, Bloomington, IN 47403, or online at COTAforJacobW.com. Checks or money orders should be made payable to COTA with “In Honor of Jacob W” written on the memo line of the check.

Sixteen-year-old Jacob Whitler said about his mother, Lisa, “All I can do is thank her and kiss her feet.”

Lisa donated one of her kidneys to Jacob, who was diagnosed with kidney failure as a baby and got corrective surgery but late last year started experiencing declining kidney function.

“I wanted to give him a new life. I wanted to give him the best chance at the most normal life possible,” said Lisa, a Loveland resident, about her son, who will be a junior at Mountain View High School.

Knowing how high the associated expenses are with a kidney transplant, Lisa’s friends organized a fundraising account on Jacob’s behalf through the Children’s Organ Transplant Association, a Bloomington, Ind.-based nonprofit focused on offsetting transplant-related expenses.

Donations are made to COTA on the patient’s behalf and used to cover expenses such as travel and hotel costs, co-payments and anti-rejection medications that are not covered by health insurance.

Family friend Karen Klein wanted to help Jacob and Lisa, who is a single mother of two children, so she agreed to do the publicity for the fundraising efforts.

“Some people you meet and you just have a connection,” Karen said. “You have a friendship, and you love each other.”

Jacob said when he hears Karen’s name, “I just get happy.”

“Karen’s been a second mother to me for lots of years. She’s always been there for me and my family,” he said.

The COTA fundraiser on Jacob’s behalf is for $45,000 and, with the help of several community members who did their own fundraisers, the effort has raised $14,000 so far. The fundraising, initiated June 1 to continue through May 31, 2015, has included portions of restaurant sales, a jewelry party, a card-making class and a bake sale.

“It’s just amazing that people we know and people we don’t know have stepped up and embraced his cause,” Lisa said.

Jacob was born with hydronephrosis with grade five reflux, or swelling of the kidneys with reverse flow of urine through the ureters that damaged both of his kidneys. When he was 2 days old, blood tests showed that his kidneys were failing, and the next day he had emergency surgery at Presbyterian St. Luke’s Hospital in Denver to replant the ureters, correcting the reflux issue.

For several years, Jacob had stable kidney function, but at a routine appointment when he was 10 years old, he was found to have decreased kidney function. He was prescribed six new medications, had to follow a strict new diet and was scheduled for numerous tests.

By the time he was 15, Jacob’s kidney function started declining again, and he was given the option of dialysis or a transplant.

Lisa did the required testing in late February and found that she was a match for Jacob and donated her kidney to him. They had the surgeries June 25, his at The Children’s Hospital and hers at University Hospital.

“It was from start to finish such an amazing process,” Lisa said. “We had people praying alongside us. Our prayers were answered.”

Following surgery, Jacob, who had been experiencing tiredness and difficulty in concentrating, started feeling energetic again, he said. He will have to wait until he’s fully recovered to return to martial arts, something he’s done for three years. He’s also involved in school theater and likes reading, archery and playing video games, he said.

“I just have a lot more energy. I don’t feel any symptoms or anything,” Jacob said.

Lisa, as the donor, felt some tiredness after surgery but is now recovered, she said.

“As a mother, I would give anything for my children,” Lisa said. “This is a gift I could give. It’s giving him new life.”

Contact Reporter-Herald Staff Writer Shelley Widhalm at 970-669-5050 or swidhalm@reporter-herald.com. Follow her at twitter.com/ShelleyWidhalm.

via Fundraisers set for double kidney transplant recipient – Loveland Reporter-Herald.

Naturally occurring antibodies may be treatment for BK nephropathy in kidney transplant patients – Medical News Today

Friday 1 August 2014 – 2am PST

A viral infection known as BK that commonly causes kidney transplant dysfunction in patients taking high doses of immunosuppressants may be treated with naturally occurring antibodies that already are widely available, according to UPMC-led research that was presented this week at the World Transplant Congress in San Francisco.

The BK virus infects most healthy children in the U.S., but the infection is usually asymptomatic and readily cleared by the immune system. However, following natural infection, latent virus persists in the kidneys for an indefinite time because antibodies in the plasma and circulating T-cells remain at levels that are high enough to prevent virus reactivation.

“However, if the immune system is suppressed – for example by kidney transplant medications designed to prevent rejection of the organ – viral infection flares up and damages the kidney. This causes a condition called BK virus nephropathy,” said Parmjeet Randhawa, M.D., a UPMC pathologist and professor of transplant pathology at the University of Pittsburgh, who led the research. “Currently, there are no anti-viral drugs or vaccines specifically designed for BK nephropathy, and none is likely to be licensed for at least the next 10 years.”

Dr. Randhawa and his team found that anti-BK antibodies are present at very high levels in immunoglobulin preparations currently being used to treat other viral infections, as well as immunologic disorders such as antibody mediated rejection of transplanted organs. These antibodies interact with a BK virus surface protein called VP-1 and effectively neutralize the virus. Such neutralized viruses can no longer infect human cells.

“By artificially constructing viruses varying in the composition of the proteins on their surface, we have shown that this neutralizing action is effective against all six common BK virus strains circulating in human populations,” Dr. Randhawa said. “These findings open the way to conduct clinical trials for preventing and treating BK nephropathy in kidney transplant patients.”

As the proposed immunoglobulin preparations are natural products derived from healthy human subjects, associated side effects are expected to be minimal, Dr. Randhawa said.

Collaborators on the study were Diana Pastrana, Ph.D., and Christopher Buck, Ph.D., both of the National Cancer Institute; Gang Zeng, M.D., of the University of Pittsburgh Department of Pathology; Mel Berger, Ph.D., of CSL Behring, in King of Prussia, Pa.; and Sundaram Hariharan, M.D., and Ron Shapiro, M.D., both of UPMC.

via Naturally occurring antibodies may be treatment for BK nephropathy in kidney transplant patients – Medical News Today.

APA
UPMC. (2014, August 1). “Naturally occurring antibodies may be treatment for BK nephropathy in kidney transplant patients.”Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/280431.php.

Protein May Prevent Antibody-Mediated Transplant Rejection

Thu, 07/31/2014 – 8:40am

A study presented at the 2014 World Transplant Congress evaluated the safety and efficacy of CSL Behring’s C1 Inhibitor (C1-INH) concentrate in preventing antibody-mediated rejection following kidney transplants in highly sensitized patients. C1-INH is a human protein and an important inhibitor of the complement system.

The study shows that post-transplant treatment with C1-INH results in significant increases in the levels of complement components 3 and 4, suggesting that C1-INH inhibits activation of the complement system following transplantation. Antibody-mediated rejection is a major cause of kidney transplant failure and is often associated with activation of complement, a set of proteins that work with antibodies and play a role in the development of inflammation and tissue damage.

“Antibody-mediated rejection is a severe form of rejection that can occur in patients who have undergone a kidney transplant,” said Stanley Jordan, M.D., Kidney Transplant, Cedars-Sinai Medical Center in Los Angeles, and one of the study’s investigators. “Our findings provide additional insight into how C1-INH affects complement activation and represent an important advance in the study of complement-targeting therapeutics.”

The placebo-controlled, single-center study evaluated 20 highly sensitized patients, meaning they already had antibodies against donor organs. Subjects were randomized to receive either placebo or 20 IU/kg of C1-INH, administered intra-operatively, then twice a week for seven additional doses. Patients were desensitized with immunoglobulin and rituximab, decreasing the patient’s antibody levels prior to transplant.

According to study findings, fewer patients who were administered C1-INH developed serious adverse events compared to those administered placebo (20% versus 30%). C1-INH function and antigen levels in blood increased with C1-INH treatment [C1 function (p=0.0007) and C1-INH antigen percent (p=0.013)]. Patients treated with C1-INH experienced increased C3 levels on day 30 (p=0.005), while C4 levels were significantly higher at all time points. During the study period, no patient treated with C1-INH developed antibody-mediated rejection. Twenty percent of patients developed antibody-mediated rejection following the study period. Thirty percent of patients treated with placebo developed antibody-mediated rejection, 10% during the study period.

Date: July 30, 2014

Source: CSL Behring

via Protein May Prevent Antibody-Mediated Transplant Rejection.

Country’s youngest kidney transplant recipient | Trinidad Express Newspaper | News

By Carolyn Kissoon

Story Created: Jul 29, 2014 at 9:57 PM ECT

Story Updated: Jul 29, 2014 at 9:57 PM ECT

The Express highlighted Nyron Ramcharan’s case back in 2010, when his mother, Nanda Ramcharan, donated one of her kidneys to save his life.

Nyron became the country’s youngest kidney transplant recipient, as he was only nine at the time of the surgery.

The mother and son were described as advocates for higher donor awareness among the population, as there are still dozens more children and adults waiting for a chance at a normal life.

As she told her story with her son, Ramcharan thanked God for the chance to save her child.

She thanked the people and the doctors who made it possible and called on fellow citizens to reach out and make a difference in the life of another through the National Organ Transplant Unit.

Ramcharan told the Express that  Nyron’s renal failure came at two years of age, after a series of unexplained high fevers.

When his doctor informed the family that a kidney transplant would be his only chance at a normal life, they were at a loss but determined to make it happen.

“It seemed so out of reach at the time,” Ramcharan had said.

“He kept getting sicker and needed regular dialysis. That went on for about 14 months, by which time less than 50 per cent one of one of his kidney’s was functioning.”

Nyron continued to live through dialysis while his barely functioning kidney failed more every day.

Then tests were done to determine compatibility and the transplant from mother to son was performed.

“Actually, how it was done is that one of my kidneys was attached to one of Nyron’s,” Ramcharan had explained.

“He is such an inquisitive child and was so happy about receiving a kidney. He actually learned a lot during the past year because he was always asking questions,” she said.

Nyron responded back in 2010.

“I feel great that my Mum did this for me and I want to say thanks to her. And thanks to all the people at the hospital.”

via Country’s youngest kidney transplant recipient | Trinidad Express Newspaper | News.