TAG: "Kidney"

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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Research may lead to cure for deadly kidney disease

Biochemists solve ‘address problem’ in cells that leads to lethal kidney disease.

Carla Koehler, UCLA (Photo by Reed Hutchinson, UCLA)

Research by UCLA biochemists may lead to a new treatment — or even a cure — for PH1, a rare and potentially deadly genetic kidney disease that afflicts children. Their findings also may provide important insights into treatments for Parkinson’s disease, Alzheimer’s disease and other degenerative diseases.

Led by Carla Koehler, a professor of chemistry and biochemistry in the UCLA College, the researchers identified a compound called dequalinium chloride, or DECA, that can prevent a metabolic enzyme from going to the wrong location within a cell. Ensuring that the enzyme — called alanine: glyoxylate aminotransferase, or AGT — goes to the proper “address” in the cell prevents PH1.

The findings were published online in the Proceedings of the National Academy of Sciences and will appear later in the journal’s print edition.

In humans, AGT is supposed to go to an organelle inside the cell called the peroxisome, but for people with a particular genetic mutation, the enzyme mistakenly goes instead to the mitochondria — tiny power generators in cells that burn food and produce most of the cells’ energy — which causes PH1.

Koehler’s team demonstrated that adding small amounts of DECA, which is FDA-approved, to cells in a Petri dish prevents AGT from going to the mitochondria and sends it to its proper destination, the peroxisome.

“In many mutations that cause diseases, the enzyme doesn’t work,” Koehler said. “In PH1 the enzyme does work, but it goes to the wrong part of the cell. We wanted to use DECA in a cell model to block AGT from going to the wrong address and send it back to the right address. DECA blocks the mitochondria ‘mailbox’ and takes it to the peroxisome address instead.”

How often did it work?

“All the time,” said Koehler, a member of UCLA’s Jonsson Comprehensive Cancer Center, Molecular Biology Institute and Brain Research Institute.

For people with the mutation, the correct peroxisome address is present in AGT, but it is ignored because it is accompanied by the address of the mitochondria, which the cell reads first, Koehler said.

Koehler, who also is a member of the scientific and medical advisory board of the United Mitochondrial Disease Foundation, hopes to find out whether a similar “correct address” strategy can slow cancer down. Her laboratory has identified approximately 100 other small molecules, which she calls MitoBloCKs, that she and her colleagues are testing for their ability to combat Parkinson’s, Alzheimer’s and other diseases.

PH1 — short for primary hyperoxaluria 1 — starts at birth and is usually fatal for patients who do not receive both kidney and liver transplants. Approximately half of those with the disease have kidney failure by age 15. Koehler has presented her findings to the Oxalosis and Hyperoxaluria Foundation, which provides support for PH1 patients and their families.

Scientists’ ability to diagnose rare diseases has improved in recent years because technological advances in genomics have made it easier to identify more genetic mutations, Koehler said.

According to Koehler, to treat diseases, scientists must first understand how proteins like AGT move inside the cell. Her research, which encompasses biochemistry, genetics and cell biology, studies how mitochondria are assembled and function, how proteins enter the mitochondria and reach the right location inside cells, and how mitochondria communicate with the rest of the cell.

Her laboratory uses model systems that enable them to study the biochemistry in a way that is not possible with humans. Much of the work is conducted in yeast.

“It’s exciting that our studies in baker’s yeast, a typical laboratory model, might be able to help kids with a complicated disease,” Koehler said.

The lead author of the PNAS research was Non Miyata, a former UCLA postdoctoral fellow in Koehler’s laboratory. Co-authors included Christopher Danpure, emeritus professor at University College London; and Sonia Fargue, a former researcher in Danpure’s laboratory.

Koehler’s research was funded by the National Institutes of Health’s National Institute of General Medical Sciences (grants GM073981 and GM61721).

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CT scan is no better than ultrasound to detect kidney stones

UCSF study leader recommends change in standard practice.

Rebecca Smith-Bindman, UC San Francisco

To diagnose painful kidney stones in hospital emergency rooms, CT scans are no better than less-often-used ultrasound exams, according to a clinical study conducted at 15 medical centers and published in the Sept. 18 issue of the New England Journal of Medicine.

Unlike ultrasound, CT exposes patients to significant amounts of radiation. Although CT scans are favored by emergency-room physicians for kidney stone diagnosis, ultrasound should be used as the first step, according to senior study author Rebecca Smith-Bindman, M.D., a professor in the departments of radiology; epidemiology and biostatistics; and obstetrics, gynecology and reproductive medicine at UC San Francisco.

“Ultrasound is the right place to start,” Smith-Bindman said. “Radiation exposure is avoided, without any increase in any category of adverse events, and with no increase in cost.” Patients in the study who were first examined with ultrasound sometimes received a follow-up CT exam at the physician’s discretion.

“Our results do not suggest that patients should undergo only ultrasound imaging, but rather that ultrasonography should be used as the initial diagnostic imaging test, with further imaging studies performed at the discretion of the physician on the basis of clinical judgment,” the study authors said.

Kidney stone rates are increasing, and in a 2010 National Health and Nutrition Examination Survey, one in 11 people reported having had at least one kidney stone. The use of CT to diagnose kidney stones has risen 10-fold in the last 15 years. CT exams generally are conducted by radiologists, while ultrasound exams may be conducted by emergency room physicians as well as radiologists.

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Related link:
Innovation Profile: Rebecca Smith-Bindman

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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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Robot-assisted technique improves surgeons’ ability to remove kidney tumors

UCLA-led study finds the approach may shorten surgeries, could reduce risk of complications.

Schematic showing the robotic device's proper position during surgery. (Image by Eric Treat, UCLA)

Roughly 50,000 Americans are diagnosed with kidney cancer each year. Most of them have small tumors that doctors discover while screening for other health problems.

The surgeries to remove renal tumors can be difficult, particularly if the cancer is on the posterior side of the kidney and if patients have had previous abdominal surgery, because scar tissue from previous operations usually makes it hard for surgeons to distinguish the normal parts of the body from one another.

Now, a study led by Dr. Jim Hu and researchers at UCLA’s Jonsson Comprehensive Cancer Center has shown that a newer surgical technique called robot-assisted retroperitoneoscopic partial nephrectomy is more effective than other current techniques to remove kidney tumors when the masses are located on the back of the kidney or when a patient has had previous abdominal surgery. RARPN is a minimally invasive laparoscopic procedure in which surgeons use precise robotic arms and magnified, high-definition 3-D cameras.

The study, published online in European Urology, was the largest multicenter study to date on this technique. The five-year project reviewed surgeries for 227 patients whose average age was 60, with most between ages 52 and 66.

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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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UC Irvine receives NIH grant to study kidney disease

Grant also will track treatment methods.

Kamyar Kalantar-Zadeh, UC Irvine

UC Irvine Health will use a $3.4 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health to examine the “Transition of Care in Chronic Kidney Disease (CKD).”

The award is one of three U.S. Renal Data System five-year contracts bestowed by the NIH upon academic centers to examine chronic kidney disease and its risk factors and consequences, including treatment modalities and outcomes of patients with CKD. The UC Irvine Health Division of Nephrology & Hypertension won a national competition to bring this prestigious grant to the UC Irvine campus.

“Our studies over the next half a decade will examine the nature and outcomes of the transition to dialysis treatment or kidney transplantation that happens in more than 100,000 Americans with advanced chronic kidney disease each year,” said Dr. Kamyar Kalantar-Zadeh, principal investigator and chief of the UC Irvine Health Division of Nephrology & Hypertension.

The award will establish the UC Irvine Medical Center in Orange as a U.S. Renal Data System Special study center for five years. The data system is a national clearinghouse for information about chronic and end-stage kidney disease and treatment modalities for these patients. It collaborates with the federal Centers for Medicare & Medicaid Services, the United Network for Organ Sharing and 18 ESRD networks across the nation.

The project will be conducted at the UC Irvine Medical Center and the Veterans Affairs Medical Center in Long Beach. The study population will consist of veterans treated at VA medical centers across the nation and members of Kaiser Permanente Southern California who are transitioning to renal replacement therapy.

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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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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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