Research

Emory Leads Research on FDA-Approved Drug in HIV Positive Patients Receiving Kidney Transplants

pearsonEmory Transplant Center will soon begin enrolling patients into a new clinical trial that will test an FDA-approved drug in HIV positive patients receiving a kidney transplant. The research study will evaluate the safety and tolerability of a drug that blocks the CCR5 receptor. The CCR5 receptor is an entry point that allows HIV into the cells of the immune system. The drug being studied, generic name maraviroc, is an antiretroviral drug that helps block the virus from entering these cells. It is currently FDA-approved for the treatment of HIV infection.

Emory will be one of ten centers across the U.S. that will be play a part in this study. A total of 130 participants with well-controlled HIV infection (must be on an antiretroviral regimen for at least three months) will be randomized into one of two study groups. In the first group, patients will receive maraviroc, with the second group receiving a placebo. Neither doctors nor patients will know if the kidney recipients are receiving the study drug or the placebo (known as the standard of care). Up to 11 participants will be enrolled at Emory.

This $1.6 million research study for all 10 sites combined is supported by the National Institute of Allergy and Infectious Diseases (ClinicalTrials.gov Identifier: NCT02741323).

“When it comes to transplanting organs in HIV positive patients, it is known that these patients have more rejection and more severe rejection than non-HIV transplant recipients,” says Thomas Pearson, MD, DPhil, professor of surgery, and executive director of the Emory Transplant Center. “This is likely because their immune systems are dysregulated and some components are overactive. This may contribute to the high rate of transplant rejection.” Dr. Pearson is the principal investigator of the Emory clinical trial.

CCR5 blockade is currently used in combination with other drugs to control HIV infection, but it has not been studied at the time of transplantation in HIV positive individuals.

“This clinical trial will help us better understand the drug’s effects on renal function at 52-weeks post-transplant and if the drug can have a dual effect in controlling the HIV infection and improving kidney transplant outcomes,” explains Dr. Pearson.

All study participants will receive immunosuppressive medications following their transplant, as any transplant patient would. Participants will be followed for up to three years after transplant.

Watch Dr. Pearson on WSB-TV discussing this clinical trial.

Belatacept Provides Better Kidney Survival Rates than Current Standard of Care

transplant drugA study of kidney transplant recipients has shown for the first time that the drug belatacept (Nulojix), which controls the immune system and prevents graft rejection, has a better record of patient and organ survival than a calcineurin inhibitor, the current standard of care.

Patients who have undergone kidney transplant are required to take medications to prevent their immune systems from rejecting their new organs. A calcineurin inhibitor (CNIs) is generally used for post kidney transplant patients, but long-term use can damage transplanted kidneys and may lead to cardiovascular disease and diabetes.

Belatacept acts as a “co-stimulation blocker,” inhibiting one of two signals the T cells need to trigger an immune response. And unlike the currently used CNIs, it is not toxic to the kidney. In fact, it helps preserve the function of the kidney over the long term and is more effective in suppressing antibodies against the kidney, which are important causes of organ loss.

Emory University School of Medicine Dean and kidney and pancreas transplant surgeon, Dr. Christian Larsen, played a key role in developing belatacept, together with Emory Transplant Center Executive Director and Livingston Professor of Surgery, Dr. Thomas Pearson. Belatacept was approved by the FDA in 2011 and is produced by Bristol Myers Squibb.

The study, called BENEFIT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial), was sponsored by Bristol-Myers Squibb and began in 2006. FDA approval of belatacept in 2011 was partly based on the first three years of results. Results from the worldwide study, led by Dr. Larsen and University of California San Francisco kidney transplant surgeon, Dr. Flavio Vincenti, were published in the Jan. 28 issue of the New England Journal of Medicine.

The seven-year, multi-center study showed that kidney transplant recipients taking belatacept experienced a rate of mortality and graft loss significantly lower than patients taking a CNI-based regimen. The risk of death or loss of the transplanted kidney after seven years was 12.7 percent for belatacept, compared to 21.7 percent for cyclosporine A.
“While the best uses of belatacept still need additional definition, these results indicate that using belatacept as standard of care has the potential to improve long-term outcomes that matter to patients,” says Dr. Larsen.

Belatacept is given by infusion monthly at a doctor’s office, in contrast to CNIs, which are taken in daily pills at home. Many U.S. insurance companies now cover belatacept as medically necessary for kidney transplant patients.

Improving Dialysis Patients’ Lives Through Kidney Transplantation

Emory Transplant Center continues to be a leader in research by studying ways we can better bring the benefits of kidney transplantation to Georgia residents. Several Emory studies have documented that receiving a kidney transplant before dialysis, or soon after beginning treatment, can improve patient outcomes and quality of life.

A recent study conducted by the Emory Transplant Center, along with two other healthcare systems in Georgia and the Southeastern Kidney Transplant Coalition, looked at why patient referral rates from dialysis centers to transplant facilities were so low. They found that three-quarters of Georgia patients on dialysis were not even being evaluated for a possible kidney transplant within their first year of dialysis.

“The study found that fewer than 28% of Georgia dialysis patients were referred to one of the state’s three adult kidney transplant centers within a year of starting dialysis,” reports Dr. Stephen Pastan, Medical Director, Emory Kidney Transplant Program, reports.

Georgia has the lowest kidney transplant rate in the country. U.S. regulations require that all dialysis centers in Georgia inform patients of kidney transplantation as a treatment option within 60 days of starting dialysis. Yet the study identified 15 Georgia dialysis facilities that referred zero patients within one year of dialysis start. The dialysis facilities with the lowest transplant referral rates were more likely to be non-profit, have more patients, and a higher patient-to-social worker ratio. Kidney transplantation is a typically less expensive intervention than ongoing dialysis and one that also promises greater longevity and a better quality of life.

One of the first key steps for many patients to receive kidney transplantation is to hear about its life-changing benefits at a dialysis center. This study illustrates the need for further measures to improve overall referral of patients to kidney transplantation.

Learn more about the Emory Kidney Transplant Program or call us at 1-855-EMORYTX (366-7989)

Flu Vaccination Proves to Reduce Rejection in Transplant Recipients

transplant_7-30-200x300Although we are currently in the throws of summer heat, schools will be starting back in the next few weeks and soon the Fall season will be upon us. With that begins flu season. The Emory Transplant Center has always encouraged our patients to get their flu shot early on in the season, and now a research study has proven it to be most effective in reducing rejection. A recent Emory study presented at the Emory Transplant Center shows that a flu shot in the first year post-transplant reduces rates of hospitalization for recipients of all organ types. The study also proved that vaccination reduces acute rejection rates among transplant recipients.

“We designed our study to compare the clinical outcomes between solid organ transplant recipients [lung, heart, kidney, and liver] at Emory University Hospital who receive flu vaccination with those who didn’t,” says Dr. G. Marshall Lyon III, Associate Professor of Medicine and Director of Transplant Infectious Diseases.

The investigators reviewed the charts of 586 recipients who received transplants from January 1, 2011 to September 1, 2012. They studied a cohort of patients who received flu vaccines during the first full flu season after their transplants and compared it to a cohort of non-vaccinated patients. The researchers collected the outcomes from each recipient for one year beginning with the start of the first full flu season – September 1st – after their transplants.

The study showed the recipients had an overall vaccination rate of 59.3%. The rate of hospitalization per patient year was lower in the vaccinated group, with 0.34 admissions per patient year for the vaccinated group and 0.51 admissions per patient year in the non-vaccinated group. When rejection episodes that were diagnosed on the date of vaccination were removed from the vaccinated group and attributed to the non-vaccinated group, there was a significant reduction in the rate per patient year, with a rejection rate of 0.13 for vaccinated patients and 0.22 non-vaccinated patients.

Learn more about the Emory Transplant Center.

Finding a Better Antifungal Agent for Lung Transplant Patients

Transplant_7-16Because human airways are open to airborne fungal spores and pathogens, lung transplant patients are especially susceptible to infections, a major cause of post-transplant disease and even death. A reliable means of preventing fungal infection in lung transplant patients is the drug posaconazole. Even though it serves well for preventing infection, the oral suspension has poor bioavailability, or absorption into the bloodstream, and patients need to have low gastric pH and high dietary fat intake for adequate systemic exposure.

In November 2013, the FDA approved a new formulation, a posaconazole extended-release tablet, which doctors at Emory Transplant Center began prescribing to patients because of its predictable absorption and improved systemic exposure.

“The purpose of the research study was to compare the oral suspension with the extended-release tablets and determine the likelihood of achieving therapeutic posaconazole levels, which provides the optimal benefit for patients,” says Michael Hurtik, clinical pharmacist for the heart and lung transplant programs, who was the first author on the study. He and the team’s pulmonologists, including Emory Lung Transplant Program medical director, Dr. David Neujahr, looked at data from a cohort of Emory Transplant Center patients who received single or bilateral lung transplantation between January 2013 and October 2014, and were treated for four months post-transplant with nebulized amphotericin and posaconazole oral suspension or the extended-release tablets.

The results showed that the use of the new posaconazole extended-release tablets resulted in therapeutic blood levels for fungal prophylaxis more often (87% of patients) than the oral suspension formulation (39%). The lung transplant patients studied also tolerated the tablets well and no one needed a dose reduction or discontinuation of the medication. This study was successful in finding a better antifungal agent for our lung transplant patients that also provides the most optimal health benefit.

Learn more about the Emory Transplant Center.

Emory Transplant Center Receives Grant to Help Increase Access to Living Donor Kidney Transplants

Living Kidney Donor Transp;lantThe Carlos and Marguerite Mason Trust has awarded the Emory Transplant Center a $500,000 grant over two years that will go a long way toward saving lives and increasing access to the benefits of living donor kidney transplants among Georgians. The grant will help Emory Transplant Center researchers design, implement and evaluate new recruitment and retention tools in partnership with Tonic Health, a leading medical data collection system. The initiative’s goals are to help living donor candidates navigate the donation process and to be able to easily track them through the entire transplant process.

“Due to enhanced awareness in the community, an increase in accessibility and various educational initiatives there are more end-stage renal disease [ESRD] patients in Georgia coming forward as potential candidates for transplantation,” says Dr. Thomas Pearson, executive director of the ETC. “Both the number of available deceased donor organs and living donor kidneys for ESRD patients have plateaued in the last three or four years, making the need to explore new techniques to increase the donor pool more urgent than ever.”

Because of this, the Emory Transplant Center has started a pilot project to capture patient questionnaires and intake notes electronically to help speed the evaluation process. The new system will flag patients who could be appropriate candidates for kidney donation based on criteria developed by our researchers and will help reduce the time nurse coordinators need to review records. It will be much more patient friendly and efficient than current phone call screening processes. The new technology will be one of the most innovative electronic screening systems for facilitating living donor kidney transplantation available anywhere in the country.

With the help of the Mason Trust grant, the Emory Transplant Center hopes to increase the number of kidney transplant evaluations by at least 30%, and decrease the time from referral to donation by 20%.

According to Dr. Pearson, “We are truly grateful for the dedication of the Carlos and Marguerite Mason Trust to help ESRD patients and their families learn about the benefits of transplantation, assist them in the transplant process, help them find living donor matches, and enable our faculty and staff to monitor their progress.”

iCHOOSE Kidney – An Education App for Prospective Kidney Transplant Patients

iChoose Kidney AppFor patients suffering from end-stage renal disease (ESRD), there are two major treatment options: dialysis and kidney transplant. Of these two options, medical studies have shown that receiving a kidney transplant offers a better chance of survival and quality of life, eliminating the need for hours of dialysis treatment.

Although it is required by law for clinicians or physicians to discuss kidney transplant as a treatment option for their ESRD patients, Emory epidemiologist Rachel Patzer, PhD, MPH, assistant professor of surgery, says that many eligible patients are not being referred for kidney transplantation. Through her research, Patzer found that such disparities were often present in regions outside the Atlanta area.

“There are disparities in who is getting access to that information about transplant, which I think is leading to some of the disparities we see in access to getting on the waiting list and receiving a transplant,” Patzer says.

In order to address these treatment disparities and help patients understand the best treatment option for their individual cases, Patzer and the Emory transplant team created the iCHOOSE Kidney iPad application. The iCHOOSE Kidney app is a shared-decision making tool for providers or clinicians to use with their patients to inform them about potential risks and benefits of each treatment. “The app basically walks you through different risks for treatment options,” Patzer says.

While Patzer says the optimal treatment for kidney disease is transplant, she says this depends on patients’ individualized risk profile, which includes factors such as their age and other possible medical conditions they may have.

Upon a patient’s initial diagnosis of end-stage kidney disease, physicians or clinicians can enter in patient data into the iCHOOSE Kidney app, which in turn calculates the risks of dying on dialysis versus a kidney transplant. The app calculates both relative and absolute risks based on data from a national database of almost 700,000 patients.

The app tries to keep things simple for patients by presenting data in a picture format. Patzer says illustrating information visually is one of the best ways to convey risks to patients. “Showing patients you’re going to live this many years longer or that this is 10 times better is really more powerful than just giving them the average,” Patzer says.

The app is currently being used at the Emory Transplant Center and in the surrounding community. Patzer says that the Emory transplant surgeons and nephrologists use the iCHOOSE Kidney app as part of their communication and education with patients. You can find the iChoose Kidney app by searching your App Store.

Lung Transplants Received from Heavy Drinkers Linked to Higher Complication Risks

Drinking in Transplant DonorsIn a recent study published in the journal Alcoholism: Clinical & Experimental Research, researchers suggest that lung transplant recipients who received lungs from donors who were heavy drinkers may be more likely to develop higher complication risks.

The study looked at 173 lung transplant patients. Of the 173 participants, 1/4 of them received lungs from heavy drinkers. Heavy drinking, according to the researchers, was defined as more than three drinks a day or seven drinks a week for women, and more than four drinks a day or 14 drinks a week for men.

When researchers compared patients who received lungs from nondrinkers, those who received lungs from heavy drinkers were nearly nine times more likely to develop a complication called severe primary graft dysfunction (PGD).

PGD is a syndrome of acute lung injury that generally occurs within the first 72 hours after lung transplantation, and may lead to an increased risk of rejection.

Dr. David Guidot, of Emory University School of Medicine, said the findings raise “the question as to whether or not a history of heavy alcohol use by a potential donor should exclude the use of their lungs in transplantation. At a time when there is a critical shortage of lungs available for transplantation, this is obviously a problematic issue,” he said.

Guidot added that if other studies confirm these findings, the lung transplant community would have to address this issue. Excluding donor lungs from heavy drinkers is one option. But he also suggested that it is possible that a drug might be developed to counteract the effects of alcohol abuse on the lungs.

Transforming Lives Through Transplant Research

Transplant Research at EmoryResearch conducted at the Emory Transplant Center over the years has led to medical and surgical treatments that restore the lives of an ever increasing number of transplant patients at Emory and beyond. And fiscal year 2013 was no less spectacular.

The 50 Emory Transplant Center faculty researchers and their postdoctoral students and staff stretched each research dollar to the limit, and created a lot of bang for the buck. They published 82 papers in 52 journals in fiscal year 2013, and twenty-eight faculty were principal investigators on an active award. Leading research faculty members — Drs. Stuart Knechtle, Allan Kirk, Leslie Kean, Ken Newell, and Ken Brigham — had a total of $11.9 million in funding last year to develop many advances. We are truly shaping the field.

Even with the recent government shutdown, the future of transplant research here in FY2014 looks positive. “Despite the worst year in federal research funding since 1931, the Emory Transplant Center is currently enrolling in the largest number of clinical trials in our history — 29 studies,” Carlson says, “Also, the ETC is the leading site in the country enrolling patients in a hepatic support device trial, which is directed by Dr. Ram Subramanian.” Overall, ETC faculty are participating in 45 kidney, liver, islet, composite tissue, lung, and heart transplantation and infectious disease research studies. And Emory’s transplant biorepository core is involved in 39 multicenter studies.

“In the end, the single most important factor is that the ETC has been able to sustain a high impact research portfolio that spans basic, translational, and clinical science research,” Carlson says. “We continue to be exceptional stewards of the investments entrusted to us. Congratulations to everyone involved in research for making such a big impact in FY2013, and thank you for your continued dedication to advancing the field.”

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Transplant Patients Need Protection Against the Flu

Flu transplant patientsWith winter only a few months away, flu season is rapidly approaching. The flu, or influenza, can be deadly for transplant patients. Because you have a chronic disease and/or are now taking anti-rejection medication, you are at an increased risk of getting the flu.

Research has shown that flu vaccination is the most effective way to reduce complications and deaths related to influenza. Don’t be caught without your flu shot!

If you had your transplant at least three months ago, it’s time to roll up your sleeve and get protected now. If you have not hit three months yet, be sure to ask for it during your three-month follow-up visit. To protect you even further, others in your household should also get flu shots or FluMist. (NOTE: Transplant patients should receive an injectable vaccine, a shot, and not FluMist [administered through the nose], which is a live flu vaccine).

Please be advised that it may take up to two weeks after getting vaccinated to build up your protection, so sooner (after three months post-transplant) rather than later is best!

In the past, if you avoided the flu shot because you are allergic to eggs, there is good news. This year, for egg-allergic individuals, there is a non-egg-based flu vaccine so you too can be vaccinated. Talk to your doctor or coordinator to learn more.

It’s time to roll up your sleeve, and take your family or housemates with you to get their shots as well. Make a commitment to get your flu shot to ward off the flu this year. We, at the Emory Transplant Center, are all getting our shots to protect you as well.

Remember, we’re all in this together.