TAG: "Transplants"

Blood test predicts signs of acute rejection in kidney transplants


UCSF finding could lead to earlier detection, treatment and improved organ survival.

Researchers at UC San Francisco have developed a potential test for diagnosing and predicting acute rejection in kidney transplants, a finding that eventually could replace the need for biopsies and lead to earlier detection and treatment.

The study is in today’s (Nov. 11) issue of PLOS Medicine.

“We have found a set of genes in blood that pick up inflammation and acute rejection in different solid organ transplants and thus can replace the need for an invasive biopsy in the future,” said senior author Minnie Sarwal, M.D., Ph.D., professor of transplant surgery at UCSF. “This assay also predicts the onset of histological rejection by three to four months, meaning graft inflammation can be treated early and proactively, even reversed.”

“This is the first assay of its kind that can provide a sensitive readout of very early rejection and inflammation in the organ, which cannot be picked up by any other blood test on the market,” Sarwal continued. “The result is improved graft function and survival.”

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Bonded by love and life-saving transplant


Lisa Flowers donated a kidney to give her daughter a normal adolescence.

Kaylyn Flowers experienced kidney failure at just 10 years of age, but returned to a fairly normal adolescence after an organ donation from her mother, Lisa.

Lisa Flowers knew her 10-year-old daughter Kaylyn’s fatigue wasn’t normal, but the urgent call from the local doctor still took her aback.

Physicians had been testing the girl to determine if a recent eye problem was due to an autoimmune disease, and they hadn’t given Lisa reason to think anything was seriously wrong. Now they reported that Kaylyn’s kidneys had been failing, quietly but completely, and that she would likely require a transplant.

“It’s one of those moments in your life that you’ll always remember, one of those life-changing phone calls,” Lisa said. “The doctor said, ‘She won’t die from this, and we’ll do everything that we can, but it’s really serious and we need her seen within the hour. Go pack, and I’ll call you back.’ ”

Yet thanks to her mother’s love, Kaylyn would return to a fairly normal adolescence within just five months. Testing revealed that Lisa was a match to donate a kidney to her daughter, a major undertaking but one that would spare the girl years of disruptive dialysis treatments.

UC Davis’ nationally renowned nephrology and transplant programs were available to perform the procedure a short drive from the family’s Roseville home.

“Everything fell in line perfectly for us,” Lisa said. “The transplant team responded right away when we said dialysis was not for us. They came immediately, started the workup and it couldn’t have gone any easier.”

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Potential blood test uncovered for disorder than can accelerate organ failure


Discovery could allow for customized therapies, improved patient selection for transplant.

Researchers at UC San Francisco and Rush University Medical Center, Chicago, may have found a predictor for a disorder affecting kidney transplant recipients that can accelerate organ failure, a discovery that eventually could allow for customized therapies and improved patient selection for transplant.

The study of focal segmental glomerulosclerosis (FSGS), a devastating form of kidney disease, is in today’s (Oct. 1) issue of Science Translational Medicine. Research was conducted by an international study team, with Necker Hospital in Paris and UCSF joint lead authors and Rush University Medical Center and UCSF joint senior authors.

“This is a new blood test to monitor patients before kidney transplant and predict who may have recurrence of FSGS, thereby preventing loss of kidneys,” said co-senior author Minnie Sarwal, M.D., Ph.D., professor of transplant surgery at UCSF.

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Teens help family of girl with liver cancer


Westside teens ‘aiming to do good wherever good can be done’ aid UCLA patient, her family.

David Mezquita kisses his 4-year-old daughter Vicky, who has liver cancer and is undergoing treatment at Reagan UCLA Medical Center. To help the family pay for nursing care, an organization of Westside teenagers raised money through a garage sale.

When Myra and David Mezquita of the South Bay had triplets, they knew they were blessed even though they had their hands more than full caring for the new arrivals as well as their teenagers.

Then one of the triplets, Vicky, was diagnosed with liver cancer and needed a transplant, which was performed at UCLA in April 2013 by Dr. Ronald Busuttil, distinguished professor and executive chairman of the UCLA Department of Surgery. Things seemed to be going well at first. But sadly, less than a year later, Vicky was diagnosed with recurrent cancer in her new liver.

To eradicate some liver tumors that remained unaffected by the chemotherapy, the 4-year-old underwent chemotherapy and stereotactic body radiation therapy (SBRT), a newer radiation treatment that noninvasively focuses high doses of radiation to kill tumors in a few treatment sessions.

The Mezquitas were juggling treatment appointments and caring for their other children when they lost crucial supplemental funding they had used to pay for nursing care for Vicky. Piling onto the family’s troubles, a utility-sparked fire that occurred about the time of Vicky’s transplant destroyed their backyard, including all the fencing and landscaping, leaving the children no safe place to play. Because of Vicky’s need for intense care following the transplant, no repairs were ever made, said her mother Myra Mezquita.

Members of Teamwork Makes the Dream Work join medical staff and family members at Vicky Mezquita's bedside in Reagan UCLA Medical Center.

Fortunately, some Westside teens who raise money to help sick children through a charity they co-founded, Teamwork Makes the Dream Work, found out about the family’s plight. Guided by the organization’s motto, “Aiming to do good wherever good can be done,” they held their annual garage sale and raised more than $5,100 for Vicky’s family, money that will help them augment her nursing care and create a new backyard for Vicky and her siblings to enjoy.

“We went all over the Westside, from Santa Monica to West Hollywood, gathering donations for the garage sale,” group member Nahal Shakib, 19, of Pacific Palisades said. “It was really important to us to raise a lot of money.”

Shakib and three members from Brentwood — Jasmine Shaouli, 18; Leila Aframian, 17; and Devon Shalom, 17 —  recently presented a check to David Mezquita, who was visiting his daughter while she was in Reagan UCLA Medical Center because of a low white blood cell count caused by the chemotherapy. The teens also brought gifts for Vicky’s siblings as well.

Dr. Julie Kang, a resident in the Department of Radiation Oncology, was able to connect the teens with the Mezquita family through a mutual friend. Kang was there when the check and gifts were presented to the family, along with Vicky’s radiation oncologist, Dr. Percy Lee, who oversaw the radiation treatments, and nurse Adriana Grandpre-Aguiar, who assisted with her care.

“It takes a lot of help to make good things happen,” the grateful father said. “I’m very happy and pleased that everyone joined together as a team to make this happen. I’m very touched.”

Myra Mezquita said that, at times, the circumstances her family is dealing with are “beyond imaginable. I can’t express the magnitude of our gratitude for the support we received from everyone.”

Lee, an associate professor of radiation oncology and director of UCLA’s SBRT program, said he was pleased they were able to treat all the visible cancer with the new radiation therapy. “This little girl has been through a lot in the last four years, and we are hopeful that the treatments give her a fighting chance,” he said.

Lee added that he was glad the family was getting some financial assistance. Even with their money woes, he said, the Mezquita family had recently given him a thoughtful gift card to pay for his lunch at a local eatery.

Kang said it was difficult watching the Mezquitas guide their child through a second bout of liver cancer.

“Parents can sometimes feel so alone in this big battle,” she said. “It’s beyond amazing that these angels came out of nowhere to help them out.”

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Seeing the future: Whole eye transplant under development


Could be ‘holy grail’ for vision restoration.

Jeffrey Goldberg, UC San Diego

The concept of a whole eye transplant seems futuristic, if not impossible. But with a $1 million grant from the U.S. Department of Defense, researchers at UC San Diego School of Medicine hope to someday make implantation of an entire, functional eye a reality.

“A whole eye transplant could be a holy grail for vision restoration,” said Jeffrey Goldberg, M.D., Ph.D., professor of ophthalmology and grant co-recipient with colleagues at University of Pittsburgh Medical Center and Boston Children’s Hospital/Harvard University. “It is in the realm of scientific plausibility.”

The basic idea is straightforward: Doctors would implant a donor eye in the recipient’s eye socket. The vascular system to the eye would be re-established, as would the eye’s musculature to enable normal movement. The greater challenge – and focus of the two-year project – would be devising effective methods to reconnect the eye’s neuronal wiring to the brain through the optic nerve, which contains more than 1 million nerve cells and transmits visual information from the retina.

Past experiments at University of Pittsburgh Medical Center have demonstrated the ability to perform whole eye transplants in genetically inbred rats (selected to minimize issues of tissue rejection). But while retinal tissue in the transplanted eyes appeared healthy, the optic nerves did not recover and regenerate connections, eliminating the possibility of restored sight.

“We know from previous experiments that the biggest scientific hurdle is not hooking up all the eye’s tiny blood vessels or its musculature,” said Goldberg, who is also director of research at UC San Diego Shiley Eye Center. “It’s that when you cut the optic nerve, the nerve cells do not regrow.”

“Our goal for this project is to be able to transplant a whole eye in an animal model and successfully demonstrate neuronal regrowth from the donor’s eye to the recipient’s optic nerve,” he said.

Researchers at UC San Diego and Harvard University have developed a variety of molecular techniques for enhancing optic nerve regeneration. One of the primary objectives is to assess whether these different techniques can be combined for greater therapeutic effect.

Among the most promising is restoring the embryonic ability of adult nerve cells to grow and blocking production of molecules that squelch nerve cells’ initial intrinsic regenerative properties. This loss of regenerative capacity is similar to what happens in spinal cord injuries that result in permanent paralysis.

Scientists have also identified proteins in the optic nerve known as neurotrophic factors that are involved in growth, survival and maintenance of developing neurons and have developed techniques for enhancing their signaling to nerve cells. Other “molecular tricks” will be used to try to overcome the inhibitory environment for re-growth normally found in the optic nerve.

If successful, researchers suggest whole eye transplants might restore sight in a wide range of patients who are blind due to structural or functional problems in the eye. For example, an estimated 120,000 Americans are blind due to damage to their optic nerves caused by glaucoma.  An estimated 186,855 eye injuries were incurred by deployed U.S. military personnel from 2000 to 2010, usually related to traumatic brain injury. Some of these cases might be remedied through eye transplants in the future.

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Pediatric transplant recipients, families celebrate at UCSF picnic


19th annual picnic points to growing success of organ transplants.

About 300 transplant recipients, donors and family members attended the 19th Annual Chris Mudge UCSF Pediatric Transplant Picnic on Aug. 23.

On a bright summer Saturday, dozens of children and their family members gathered at McNears Beach Park in San Rafael, listening to music, kayaking, having their faces painted, smashing piñatas, even playing with costumed Smurfs. For this group, the outlook wasn’t always this sunny.

The children are part of a special group: they’re pediatric transplant recipients from UCSF Benioff Children’s Hospital San Francisco.

The 19th Annual Chris Mudge UCSF Pediatric Transplant Picnic on Aug. 23 gave children who received transplants from UCSF and their families an opportunity to come together for support, to share knowledge and to celebrate having another chance at life. The 300 attendees included those who had received pre- and post-liver, kidney and small bowel transplants, as well as physicians, transplant surgeons, nurses and others from the UCSF Transplant Service.

“Some of my patients now are married and come to the picnic,” said Phil Rosenthal, M.D., former medical director of the pediatric liver transplant program and current director of pediatric hepatology at UCSF. “A lot of our families look forward to coming back to this picnic each year to reconnect.”

One of those returning patients was Justin Erickson of Redwood City. In 1992, he needed a liver transplant due to biliary atresia, a life-threatening condition in which the bile ducts are blocked.

Twenty-two years later, the 31-year-old city of San Carlos employee is a husband and father of a 5-month-old daughter.

“The first five years after the transplant, it was a real rough battle,” said Erickson, who has attended every picnic. “I had a lot of ups and downs, but I’m doing pretty good now. It’s amazing all the things I’ve accomplished and the goals that I’ve met after the transplant.”

In sharing his personal experience, Erickson has advice for pediatric patients and their families awaiting a transplant at UCSF.

“If you are looking to have a transplant at UCSF, hold your hopes up,” he said. “You definitely are talking to the right caregivers. Benioff Children’s Hospital San Francisco is the place to be with the cutting-edge technology and the doctors that have the know-how.”

Erickson is living proof of the growing success of organ transplants. Before, a 50-percent success rate was considered satisfactory. Now, thanks to medical advances and improved immunosuppressive drugs to combat infection and rejection, more than 90 percent of transplant patients are surviving, including children.

Founded in the 1960s, the UCSF Transplant Service is a world leader in clinical transplantation and has developed innovative techniques while producing superior outcomes. UCSF began pediatric kidney transplants in 1964 and pediatric liver transplants in 1989, making it among the oldest children’s transplant services in the country.

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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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