TAG: "Transplants"

New mouse model points to therapy for liver disease


UC San Diego findings could have impacts on obesity, organ transplantation.

Non-alcoholic fatty liver disease (NAFLD) is a common affliction, affecting almost 30 percent of Americans, with a significant number suffering from its most severe form, called non-alcoholic steatohepatitis or NASH, which can lead to cirrhosis and liver cancer. In recent years, NASH has become the leading cause of liver transplantation.

Development of effective new therapies for preventing or treating NASH has been stymied by limited small animal models for the disease. In a paper published online in Cancer Cell, scientists at the UC San Diego School of Medicine describe a novel mouse model that closely resembles human NASH and use it to demonstrate that interference with a key inflammatory protein inhibits both the development of NASH and its progression to liver cancer.

“These findings strongly call for clinical testing of relevant drugs in human NASH and its complications,” said senior author Michael Karin, Ph.D., Distinguished Professor of Pharmacology in UC San Diego’s Laboratory of Gene Regulation and Signal Transduction. “Our research has shown that, at least in this mouse model, chemical compounds that include already clinically approved drugs that inhibit protein aggregation can also be used to prevent NASH caused by a high-fat diet.”

The increasing prevalence of NAFLD is linked to the nation’s ongoing obesity epidemic. In the past decade, the rate of obesity has doubled in adults and tripled in children, in large part due to a common diet rich in simple carbohydrates and saturated fats. NASH is characterized by inflammation and fibrosis, which damage the liver and can lead to cirrhosis, hepatocellular carcinoma (HCC), the major form of liver cancer, and loss of function. Often, the only remedy is organ transplantation.

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Improving long-term health of kidney transplant recipients


UCSF is lead institution on $17M multicenter study to improve long-term survival.

Flavio Vicenti, UC San Francisco

UC San Francisco is the lead institution on a new seven-year, $17 million multicenter study funded by the National Institutes of Health to determine if certain immune system cells and/or a drug now used for treating rheumatoid arthritis can be effective in improving and maintaining the long-term health of kidney transplant recipients.

The goal of this study is to reduce or eliminate inflammation in kidney transplants and prevent the associated decline in function, thereby maximizing long-term organ survival. It will involve two clinical trials and research in parallel by biologists and by researchers for the mechanistic cores.

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 progression of interstitial fibrosis and tubular atrophy in the kidney.

The cells that the researchers are focused on are regulatory T cells (Tregs), which are 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 the University of Alabama at Birmingham, 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 – TASK (Treg Adaptive therapy in Subclinical inflammation in Kidney transplantation) and TRAIL (Therapy to Reduce Allograft Inflammation with IL6 inhibition).

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First-of-its-kind program seeks to encourage kidney donors


UCSF joins with Walgreens in blood pressure testing program for living kidney donors, potential donors.

While recipients of living donor kidney transplants receive steady follow-up care, the living donors themselves also need to be monitored. To make follow-up care more accessible, UC San Francisco and Walgreens are collaborating to launch the first program in the country that provides blood pressure testing at no charge to living kidney donors.

UCSF will provide vouchers for blood pressure tests redeemable at more than 4,500 Walgreens pharmacies and Healthcare Clinic at select Walgreens locations nationwide. Vouchers also are available to potential kidney donors, as blood pressure testing is a part of the initial screening process.

Tests are available daily during pharmacy and clinic hours with no appointment necessary and administered by health care professionals at Walgreens pharmacies and Healthcare Clinic at select Walgreens.

“The use of living donors has revolutionized kidney transplants, and this new program provides the opportunity to monitor their long-term health in a convenient, efficient way,” said John Roberts, M.D., professor of surgery and chief of UCSF Transplant Service and former president of the United Network for Organ Sharing (UNOS). “UCSF performs the most kidney transplant procedures in the United States, and we are pleased to be first to join with Walgreens in this effort that we hope encourages people to donate as there is a critical need.”

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Siblings discover relationship in time for kidney donation


Life-saving procedure performed at UCLA.

Guadalupe Villanueva and Frank Ybarra

Two people whose lives intersected at times over the last couple of decades discovered only a few months ago that they are actually brother and sister. The sister said it was nothing less than divine intervention — because it gave her the opportunity to donate a kidney to her newfound brother in a life-saving procedure that took place June 24 at the Ronald Reagan UCLA Medical Center.

“I don’t know what to say,” Frank Ybarra said to Guadalupe Villanueva as they embraced shortly before the surgery.

“You don’t have to say anything,” Villanueva said. “This is our destiny, from here on.”

“This is a step; it’s a start,” said Ybarra, who had been on dialysis due to kidney failure since September 2012.

“Yep, it’s a beginning,” she replied.

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Kidney transplant recipients meet donors for first time


Paired exchange renews the lives of four people with chronic kidney disease.

Kidney transplant donors and recipients who participated in the four-way exchange were (from left) Chris Ewing, Darrel Ellis, Steve Saunders, Olga Belozertseva, Tatiana Belozertseva, Mike Navarec, Michelle Roley and Eric Soik.

In a rare and touching moment at UC Davis Medical Center, four kidney transplant patients met the four people — strangers to them before today — who one month ago gave them the gift of life.

The transplants were the result of a process known as paired exchange, which typically occurs when a donor wants to give a kidney to a friend or family member with end-stage kidney disease but can’t due to mismatched blood types or antibodies. The donor agrees to give a kidney to a different recipient, whose unmatched donor does the same.

“Sometimes paired exchanges are completed with two pairs, and sometimes they are more complex,” said Sharon Stencel, a nurse and coordinator of the Living Kidney Donor Program at UC Davis. “In this case, someone stepped up to donate a kidney who didn’t have a particular recipient in mind. That triggered a chain of exchanges that resulted in four people — including someone on the waiting list — getting new organs and new lives.”

Given the shortage of deceased donor kidneys, paired exchange of living donors has become an increasingly important way to speed the transition from the transplant wait list to the operating room. It also can lead to better outcomes for recipients. Newer organ retrieval procedures have made the process easier for donors as well.

“While we have excellent outcomes with deceased organ donations, kidneys from living donors are viable up to twice as long — an average of 17 years versus 10,” said Christoph Troppmann, a surgeon with the UC Davis Transplant Center. “We also use less-invasive techniques for removing kidneys so scarring is minimal and recovery time is much quicker than it was a decade ago.”

One month after her surgery, donor Michelle Roley of Lockeford is “feeling wonderful” and happy that she helped restore her father’s health.

“I knew we weren’t the same blood type, but I went into the donation process hoping to be part of a paired exchange because it was the best way to help my dad,” she said.

Before the surgery, Roley’s father, Mike Navarec of Stockton, had chronic kidney disease that kept him at home for hours tethered to a dialysis machine and “worried about whether or not I would wake up in the morning,” he said. “Now, I look forward to planning a trip to the Holy Land.”

Roley’s kidney was donated to Eric Soik of Camino, who was on the transplant wait list. Navarec received a kidney from Tatiana Belozertseva of Russia. Chris Ewing of El Dorado Hills — the nondirected donor who initiated the exchange — gave a kidney to Darrel Ellis of Sparks, Nev. Steve Saunders of Reno, Nev., gave a kidney to Olga Belozertseva of Brentwood.

The UC Davis Transplant Center, which has the only kidney transplant program in inland, Northern California, has provided specialized care to kidney transplant recipients and living kidney donors since 1985. In collaboration with hospitals and transplant registries nationwide, the center has coordinated 25 paired kidney exchanges, including two four-way exchanges. Currently, there are nearly 1,200 people on a waiting list for donor kidneys at UC Davis, where more than 300 kidney transplants are performed each year.

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UCSF adult lung transplant program ranked highest for patient survival


Hospital achieves significantly better than expected outcomes.

Steven Hays, UC San Francisco

UCSF Medical Center has the highest one-year survival rate in the nation, among institutions performing more than 20 adult lung transplants each year, according to data from the Scientific Registry of Transplant Recipients (SRTR), a national database of transplant statistics.

The most recently released statistics reviewed lung transplant outcomes from July 2010 through December 2012. Based on 104 adult lung transplants, 96 percent of patients treated at UCSF Medical Center were still alive one year after surgery. The expected rate nationally is 84 percent.

UCSF Medical Center also is the only program to have achieved significantly better than expected outcomes for two consecutive report cycles from SRTR.

“We don’t shy away from complex cases. Pushing the boundaries is how we develop our expertise,” said Steven Hays, M.D., medical director of the UCSF Lung Transplant Program. UCSF Medical Center performs between 40-50 adult lung transplants annually.

Lung transplants can be among the riskiest transplant procedures, according to Jasleen Kukreja, M.D., program and surgical director of the UCSF Lung Transplantation Program.

The surface area of a person’s lungs constantly is exposed to potential airborne pathogens or toxins, which can make it harder to care for a lung transplant patient than a kidney or even a heart transplant patient.

The high survival rate is especially meaningful, since UCSF takes care of some of the sickest patients. The hospital is unusual for its willingness to accept patients who have been turned away by other medical centers, as well as for its public mission to research new approaches to treatment and share the results with other institutions.

“We figure out what works for patients who come to us with complex issues, and we report our outcomes to the broader community in hopes that others may benefit. Over time, that’s how transplant medicine improves and transforms,” Hays said.

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New organ transplant strategy aims to better prevent rejection


UCSF approach might end lifelong drug treatment.

Qizhi Tang, UC San Francisco

Organ-transplant recipients often reject donated organs, but a new, two-pronged strategy developed by UC San Francisco researchers to specifically weaken immune responses that target transplanted tissue has shown promise in controlled experiments on mice.

The hope is that using this novel treatment strategy at the time of transplantation surgery could spare patients from lifelong immunosuppressive treatments and their side effects. The approach might also be used to treat autoimmune diseases such as type 1 diabetes, the researchers said. The study is published and commented upon in a recent issue of American Journal of Transplantation.

The study was conducted in mouse studies of islet-cell transplantation — a procedure used to restore insulin secretion and control over glucose levels in the blood in patients with life-threatening diabetes. The treatment allowed more than 70 percent of mice to accept transplants without requiring any long-term treatment with immunosuppressive drugs.

The approach, led by Diabetes Center member Qizhi Tang, Ph.D., involved using cells from donors to activate immune cells called donor-reactive effector T cells. The researchers then gave the mice a drug called cyclophosphamide, known to specifically kill activated cells.

Up to 80 percent of the donor-reactive effector T cells, which play a major role in transplant rejection, were eliminated by this treatment. However, that procedure alone did not prolong survival of transplanted tissue.

That required a second step: Some of the mice also received cell therapy — an expanded population of cells called TREGs that quell immune activity. Seventy percent to 80 percent of these mice accepted the transplants, without requiring any long-term immunosuppressive drugs.

Significantly, when the cell therapy was used only in those cells that specifically target donor tissue, only one-fifth as many cells were needed to prevent transplant rejection, the UCSF researchers found. The bigger bang per cell may bode well for clinical protocols, Tang suggested.

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Blood test serves as ‘crystal ball’ for heart transplant patients


Test can predict potential rejection-related problems in the future.

Mario Deng, UCLA

A new UCLA-led study shows that a blood test commonly used to determine whether heart transplant recipients are rejecting their new organ can also predict potential rejection-related problems in the future.

Reporting in the online edition of the peer-reviewed journal Transplantation, researchers demonstrate how the AlloMap test, which uses a blood sample to measure changes in the expression of roughly a dozen genes, can be used over a period of time to assess the risk of dysfunction or rejection of a transplanted heart — months before such an event may occur.

“For the first time, we can use genomic testing over multiple patient visits to go beyond intuition to understand not just how patients are doing now but how they are likely to be a few months from now,” said Dr. Mario Deng, medical director of UCLA’s Integrated Advanced Heart Failure–Mechanical Support–Heart Transplant Program and the study’s principal investigator. “It’s another step toward personalized medicine.”

The discovery that transplant recipients’ white blood cells contain this prognostic information on rejection, independent of how their transplanted heart may be functioning currently, could potentially improve care and outcomes, the researchers said. The findings represent a significant step in the movement toward using genomic-based testing to predict future clinical events and bolster the importance of similar tests being developed for recipients of other organs.

In the U.S., approximately 2,000 patients receive lifesaving heart transplants each year, and monitoring their immune systems for signs of rejection is a critical part of follow-up care. Until recently, however, the only way to diagnose rejection was through a heart-muscle biopsy, a painful and potentially risky procedure in which a heart catheter is inserted through a vein in the neck.

That changed with the development of the AlloMap gene-expression profiling test, which received clearance from the Food and Drug Administration in 2008. The test is now routinely used by a majority of U.S. heart transplant centers to monitor low-risk patients during follow-up care, resulting in a substantial reduction in the number of biopsies.

AlloMap, which is based on research Deng led in conjunction with more than a dozen of the largest U.S. heart transplant centers and the Brisbane–based biotech company XDx, measures the expression levels of 11 genes from a patient’s blood sample, each of which is known to be associated with rejection risk.

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Lifesaving surgery makes for an extra special Valentine’s Day


Minimally invasive heart procedure followed by lung transplant.

All smiles, Mike Boyle and his wife, Ellen, are looking forward to celebrating a special Valentine's Day.

Mike Boyle has good reason to give his wife and family extra hugs on Valentine’s Day.

Just two months ago, he was slowly suffocating from pulmonary fibrosis, a condition with no cure that causes scar tissue build-up in the lungs, making it difficult to breathe. In addition, his main heart valve was so clogged with calcium deposits that it couldn’t open wide enough to adequately pump blood through his body.

Feeling exhausted, the Thousand Oaks resident had curtailed all his activities and needed to carry around an oxygen tank to help him breathe.

Given his declining heart condition, it was too risky for him to receive a much needed lung transplant, a factor that the UCLA lung transplant committee took into consideration before turning him down. Given that UCLA handles the most advanced, serious patient cases and he still didn’t qualify, it looked like Boyle had truly run out of options.

But fortunately, there was one left. The heart team at UCLA was offering a new procedure that is designed for patients who are too sick to have the conventional surgery needed to replace the main heart valve. Luckily, Boyle qualified.

The minimally invasive procedure, called Transcatheter Aortic Valve Replacement (TAVR), involves far fewer surgical risks. TAVR allows doctors for the first time to replace the aortic valve without open heart surgery. It’s an attractive alternative for patients like Boyle, who aren’t candidates for traditional surgery.

The usual TAVR approach is to deliver the valve to the heart via an artery in the groin using a catheter, which is a hollow delivery tube. But in Boyle’s case, these arteries had blockages that made this approach impossible. Alternatively, a small incision is made on the side of the chest, and the valve is delivered through the lowest part of the heart called the apex. Once in place, the valve is opened, and it starts working immediately.

Boyle had the TAVR procedure using this alternative approach last June with a heart team led by Dr. Richard Shemin, chief of cardiothoracic surgery, and Dr. William Suh, assistant clinical professor of medicine and interventional cardiology, both with UCLA’s David Geffen School of Medicine and UCLA Health System.

Boyle’s heart was doing so well after the valve replacement that he was encouraged to try to get listed again for a lung transplant. This time he was approved by the UCLA committee and received his lifesaving lung transplant in late November with a team led by Dr. Abbas Ardehali, a professor of cardiothoracic surgery and director of the heart and lung transplantation program at UCLA.

Today, Boyle is progressing nicely, say his doctors — and he couldn’t be happier.

“I don’t feel as physically limited as before and have a new lease on life,” said Boyle, who doesn’t need to carry oxygen anymore and has started to exercise as well.

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UC Davis Transplant Center opens Fresno location


Clinic will expand access to kidney, pancreas transplant care in Central California.

Luke Preczewski, UC Davis

Luke Preczewski, UC Davis

The UC Davis Transplant Center — one of the nation’s premier transplant programs — has opened a new clinic in Fresno to expand access to kidney and pancreas transplant care in Central California.

The clinic provides pre- and post-transplant medical evaluations for recipients and kidney donors. Transplant surgery will still be provided at the center’s main location at UC Davis Medical Center in Sacramento.

The Fresno clinic is located at 1189 E. Herndon Ave. and will be open one day per month. The number of clinic days will increase based on patient need. To arrange for a referral or schedule an evaluation, call toll free (800) 821-9912.

Fresno is the largest city in California without a transplant center within 25 miles, yet about 17 percent of California’s kidney transplant patients are in the Fresno region. One of the closest centers is at UC Davis Medical Center, which is about 170 miles away.

“We wanted to reduce that travel time as much as possible for patients and their families,” said Luke Preczewski, executive director of the transplant program.

UC Davis performed 339 kidney transplants in 2013, making it by volume the second-largest program in the nation. According to 2012 data from the Scientific Registry of Transplant Recipients, UC Davis offers the shortest average adult kidney transplant wait time (37.2 months) of any California hospital.

For information about the UC Davis Transplant Center, visit www.ucdmc.ucdavis.edu/transplant.

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Football fans team up for organ match


Random stadium seat assignment leads to lifesaving transplant surgery.

Louis Munoz (left) donated one of his kidneys to William Lynch - the match between the childhood friends occurred after they happened to sit next to each other at a Chargers game.

Louis Munoz (left) donated one of his kidneys to William Lynch - the match between the childhood friends occurred after they happened to sit next to each other at a Chargers game.

In October, Louis Munoz donated one of his kidneys to William Lynch. The organ match would not have occurred without a bit of serendipity and a big love of football. Munoz and Lynch had been childhood friends, but hadn’t seen each other in years – then they found themselves randomly seated next to each other at a Chargers game.

“Louis and I knew each other as kids and then lost touch. Years later, by surprise, we ended up sitting right next to each other at Chargers games,” said William, a middle school teacher. “When I started missing games, Louis asked me why and I explained that due to kidney complications, I’d been unwell. His wife half-jokingly suggested that he give me a kidney.”

Louis immediately volunteered to be tested as a possible donor. William initially declined his friend’s offer, believing another donor would come through. But when that didn’t happen, Louis followed through and proved to be a match.

“I am so blessed that Louis has chosen to give me this new lease on life,” said William. “I can’t express to him how grateful I am. I promised Louis I will take care of this kidney the best that I can.”

Prior to the transplant surgery, William had been on dialysis, a treatment option to filter the blood and rid the body of harmful wastes and excess salt and water. Dialysis is a tough regimen that requires a patient to be tethered to a machine three to four times per week for hours at a time.

“I had been on dialysis for more than two years. Mentally and physically it was the hardest part I had to endure,” said William whose kidney failure was caused by a rare disease that attacks the organ’s filtering system. “Getting off of dialysis is wonderful.”

William and Louis had their surgeries performed at UC San Diego Health System, which boasts the region’s largest kidney transplant program. The program has performed more than 2,270 kidney transplants. Approximately 35 percent of the donations come from living donors.

“In San Diego, of all the people waiting for an organ transplant, more than 85 percent need a kidney,” said Alan Hemming, M.D., transplant surgeon, UC San Diego Health System. “Living donors can dramatically shorten the time to wait for a donated kidney. The gift is truly lifesaving.”

Currently, there are more than 770 patients at UC San Diego Health System awaiting a kidney transplant. Nearly 98,000 people in the United States are on kidney transplant wait lists, including 17,784 in California. The average wait for a kidney from a deceased donor is typically six years in San Diego and ten years in Los Angeles.

The transplant surgery was performed in two phases in adjacent operating rooms. In one room, the kidney was carefully removed from Louis; in the second, it was transplanted into William.

Santiago Horgan, M.D., chief of minimally invasive surgery at UC San Diego Health System, removed the kidney aided by a robot. With robotic guidance, the vessels of the kidney were precisely isolated and the kidney was removed with less trauma. And because smaller incisions were made, the risk of subsequent pain was also reduced. Hemming then transplanted the removed kidney into William during a two-hour procedure.

“I am excited for William,” said Louis. “I think the decision to donate is pretty simple. I don’t think too much about it – just a little inconvenience to help somebody out who really needs it.”

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Award recognizes impact of anthropologist’s work on human organs trade


UC Berkeley’s Nancy Scheper-Hughes honored for watchdog role.

UC Berkeley anthropologist Nancy Scheper-Hughes is shown here talking with Alberty Alfonso da Silva in the Recife, Brazil, slum he called home before after being transported to South Africa to sell his kidney to a recipient flown there from New York City. (Photo by John Maier)

UC Berkeley anthropologist Nancy Scheper-Hughes is shown here talking with Alberty Alfonso da Silva in the Recife, Brazil, slum he called home before after being transported to South Africa to sell his kidney to a recipient flown there from New York City. (Photo by John Maier)

UC Berkeley anthropologist Nancy Scheper-Hughes has been honored by the American Anthropological Association with its first ever Anthropology in Public Policy Award for her trailblazing work shedding light on the dark practice of human organs trafficking.

The award, recognizing anthropologists whose work has had a significant and positive influence on government decision-making, was announced at a recent American Anthropological Association conference in Chicago.

In 1999, Scheper-Hughes, director of UC Berkeley’s medical anthropology program, helped found the Berkeley Organs Watch project. It monitors the organ-transplant trade for abuses among the transnational networks that connect patients, transplant surgeons, brokers, medical facilities and live donors, who often live in the poorest parts of the world.

“When I began the Organs Watch project, it was heretical to suggest that human trafficking for organs was not just a hyperbolic metaphor of human exploitation, but was actually happening in many parts of the world,” Scheper-Hughes said in her acceptance remarks.

But the project generated international headlines, particularly as Scheper-Hughes has called for more accountability from the medical profession in the field of medical anthropology. She also has been asked to testify before national and international governmental and medical panels, and has helped law enforcement agencies uncover illicit organs trafficking around the globe.

In recent years, Scheper-Hughes has advised the European Union, the United Nations and the Human Trafficking Office of the World Health Organization. She has also testified before Congress, the Council of Europe and the British House of Lords. In addition, she has consulted on several documentary as well as commercial films exploring organ trafficking.

In accepting the award, the self-proclaimed “agent provocateur” acknowledged that the complex social issues that anthropologists explore often have no single, simple solution, and one answer can prompt a new problem.

“So, yes,” Scheper-Hughes said in her speech, “I did help interrupt kidney trafficking in Moldova, only to have the international brokers use my Organs Watch website … to set up a robust scheme in illicit transplants using Afro-Brazilian men from the slums of Recife to service Israeli and European transplant tourists to South African hospitals … And, yes, I contributed to the ban on the use of executed prisoners in China as organ suppliers, only to learn that new organ suppliers could be found in China among rural village girls and Vietnamese immigrants.”

Scheper-Hughes said agent provocateurs must continue “to put their bodies, as well as their words, on the line, and work on behalf of communities and populations under siege…”

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