New life for less-than-perfect organs

Academic medical centers are pioneering innovative ways to transplant organs that might otherwise be discarded.
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Every day, 20 people die waiting for an organ transplant. Every 10 minutes, someone new is added to the United Network for Organ Sharing (UNOS) national transplant waiting list.

If you need a kidney—the organ most in demand—you might wait three to five years on the UNOS list before being matched. A liver or lung transplant could take six months to a year.  

What’s more, the number of people on the waiting list continues to far outstrip supply. In 2016, more than 115,000 Americans were waiting for an organ, but just 16,000 people donated. Yet 5,000 organs were discarded from deceased donors in 2016 alone, according to a 2017 report from the National Academies of Sciences, Engineering, and Medicine.  

“Reducing the number of discarded organs could help fill a critical need for organs.” 

Janis Orlowski, MD
AAMC chief health care officer

In light of these startling statistics, academic medical centers have been exploring new ways to boost the supply of viable organs. The use of organs from so-called marginal donors—defined as those who are older or who have diabetes, hypertension, or even infectious diseases such as Hepatitis C or HIV—has opened new avenues for research, says Janis Orlowski, MD, a transplant nephrologist and AAMC chief health care officer. So has improving the transport of organs to limit tissue damage.

“Reducing the number of discarded organs could help fill a critical need for organs,” Orlowski says.  

Waste not, want not

For years, organs from unhealthy donors were routinely rejected for fear that they could make the transplant patient more sick. But a surge in donors infected with the Hepatitis C virus (HCV) prompted researchers at the Perelman School of Medicine at the University of Pennsylvania to explore a work-around. 

HCV has a 95% cure rate after a 12-week course of medication. Researchers began to wonder: What if physicians transplanted an HCV-infected organ—with the patient’s full knowledge and consent—and then treated them for the disease later? The clinical trial team at Perelman went to the bottom of the UNOS list to enlist people waiting for kidneys.

Getting off dialysis was well worth the risk for some, says David Goldberg, MD, MSCE, assistant professor of medicine and epidemiology, who is coleading the trial. “Dialysis takes a toll on people physically and emotionally; 25% die while waiting for a donor.”

All 40 transplant patients who received HCV-infected kidneys contracted the virus but were cured of it following treatment, Goldberg reports. More important, all have functioning kidneys now that were not compromised by the infection. While still considered experimental, Goldberg says this approach could soon become standard. Other researchers at Penn are now attempting the same with HCV-infected donor hearts, and trials on liver and lung transplant patients are next. 

A South African transplant surgeon conducted a similar trial—transplanting HIV-infected kidneys into two HIV-positive patients. Elmi Muller, MB, ChB, followed the patients from 2008 to 2014, documenting the largely successful outcomes in a 2015 study published in the New England Journal of Medicine. In 2016, Johns Hopkins Medicine became the first hospital in the United States to transplant an HIV-infected kidney into a patient with HIV, and the first in the world to transplant an HIV-infected liver into an HIV-positive patient.

Friday, May 25, 2018

Educating Physicians and Patients to Ease the Donor Shortage

One donor can save up to eight lives. But physicians sometimes fail to identify possible donors or don’t know how to discuss donation effectively with families. 

“It’s a pervasive challenge in transplantation,” says Dorry Segev, MD, PhD, director of the Epidemiology Research Group in Organ Transplantation at Johns Hopkins Medicine. “People who die and could be donors are not. The more informed physicians are, the better they can counsel families and achieve a higher conversion rate.” 

In 2014, Johns Hopkins published a study showing that medical trainees at their institution had limited knowledge about the donor conversion process. Asked 10 fundamental questions about donation and transplantation, 40 residents and fellows scored an average of 5 out of 10 correctly—“a pervasive deficit” at an academic medical center, the authors wrote.

Low health literacy among patients is another problem, says Prabhakar Baliga, MD, chair of the department of surgery at Medical University of South Carolina (MUSC). “[As physicians] we focus on surgical issues but if we don’t educate patients about the living donor concept, it goes no further.” With a grant from the National Institutes of Health and the National Institute of Diabetes and Kidney Diseases, MUSC developed video programs for African American transplant patients and donors who are disproportionately affected by the donor shortage. 

“People must understand the process before they are comfortable donating organs,” echoes Janis Orlowski, MD, a transplant nephrologist and AAMC chief health care officer. “Some families are concerned that physicians will not try as hard to save a loved one’s life if the person is a donor. Hospitals must have experts available to talk to families. I try to remind families to think about what the wishes of the deceased person would be.” 

Researchers estimated in a 2017 study in Transplantation that 313 more transplants could be performed in the United States each year if patients and their families had a better understanding of the outcomes when asked if they would be willing to accept an increased risk organ.

Moving beyond the ice age 

Potentially viable organs can also be discarded because they sustain damage during retrieval or transport. For the last 50 years, organs have been submerged in a carefully prepared electrolyte solution and then put on ice during transport, but this icing and rewarming process can do irreversible damage. Hearts and lungs are particularly vulnerable, since they can only survive four to six hours outside the body. By comparison, livers are viable for 12 to 15 hours after being harvested, and kidneys can last up to 24 hours.

To reduce tissue damage, researchers at the Duke University School of Medicine are working with the makers of several ex vivo perfusion devices to perfect a machine that can mimic the environment of the human body. Rather than storing an organ on ice, ex vivo perfusion stores it at the same temperature as the human body while nutrient-rich blood taken from the donor pumps through it.

Debra Sudan, MD, professor of surgery and division chief of abdominal surgery at Duke, is the principal investigator of the liver transplant trial, and she believes ex vivo perfusion will become standard practice within a few years. 

Perfusion might expand the pool of available donors too. With the ability to preserve organs much longer during transit, patients can take advantage of donor matches from around the country. Plus, using the perfusion device allows surgeons extra time to examine the organ before transplantation, which can improve outcomes. 

What’s next? Researchers at academic medical centers are exploring the potential of animal organ transplants and using stem-cell technology to create lab-grown organs. In addition, trials on animals using a “nanowarming” technique to warm organs after cold storage could open up the possibility of banking organs someday.