The AJT Report
The AJT Report
This month, “The AJT Report” looks at dramatic changes in donor characteristics in recent years–specifi cally, the disproportionate increase in the expanded criteria donor organs. We also look at the impact of budget sequestration on the field of transplantation.
News and issues that affect organ and tissue transplantation
Public health trends and consumer safety initiatives over the past few decades have led to decreases in motor-vehicle deaths. Mandatory seat belts and helmets, enforcement of DUIs and speeding laws, improvements in automobile crash-worthiness, electronically enhanced braking systems and improved roads, in addition to developments in trauma care and the neurosurgical management of traumatic brain injuries have all contributed to welcomed declines in accidental terminal neurologic injury. This is a terrific trend for all, but nevertheless has unintended consequences for transplantation, as standard criteria donors (SCDs) now make up a smaller percentage of the pool of organ donors.
Although 2011 data from the Scientific Registry of Transplant Recipients (SRTR) show that the number of SCDs have remained about the same in the U.S. and Europe in recent years, there has been a dramatic increase in older donors and organs classified as donation after cardiac death (DCD). “The percentage of all donors who are SCD is declining and has for the last 20 years or more,” says Stephen T. Bartlett, MD, surgery department chair at the University of Maryland School of Medicine in Baltimore. He quotes SRTR data in noting that the percentage of transplanted deceased donor kidneys from donors older than age 50 increased by 216% between 1991 and 2011, while donors in the ideal age range of 6 to 49 years decreased from 76.2% of all donors to fewer than half (43.4%).
“The change in donors is similar over here,” says Christopher Watson, professor of transplantation at Cambridge University in the United Kingdom. “We have more cerebrovascular accidents and far fewer traumas than before. Donors are older, more obese and more frequently DCD.”
He adds that the situation in Europe is similar. “In Spain, where donation rates have long been the highest in the world, they have long used much older donors than elsewhere in Europe,” he says. “In Holland, there are now more DCD donors each year than donors after brain death [DBD].”
Jacques Pirenne, MD, PhD, professor of transplant surgery at University Hospitals Leuven in Belgium, agrees that the number of DCD donors is increasing, but adds that, so far, this does not seem to be at the cost of DBD, which has remained stable. “The percentage of DCD in Belgium is not as high as in the U.K. or in Holland,” he says. “DCD represents about 10% to 20% of the donor pool in Belgium. We are currently not as aggressive as the U.K. or Holland when it comes to using ‘ECD DCD’ like DCD over age 60, but we'll get there also, I presume.”
Prof. Watson notes that many countries are increasingly looking at these expanded criteria donors (ECD). “Ways that might improve the quality of preservation prior to implantation are being studied in an effort to make the most of the available organs,” he says. “There have been a few recent trials of large cold machine perfusion of kidneys in Europe, and in England there is a pilot of warm preservation of the liver.” More work in Europe is looking at normothermic regional perfusion of DCD donors, putting the donor on extracorporeal membrane oxygenation post mortem, he adds. “In Spain, this has been with category 2 donors; in the U.K., we are looking at category 3 donors with good results so far.”
- Due to advances in consumer safety initiatives and trauma care, the percentage of all donors who are SCD is on the decline, and there has been an increase in ECD donors.
- Immunosuppressant strategies and patient expectations may need to change, as this shift could impact outcomes.
- More research is necessary to improve the quality of organs used for transplant and to optimize the use of a further expanded donor pool.
“The reality of the decline of SCD kidneys means that transplant programs are going to have to rotate their immunosuppressant strategies to be far more nephron sparing than in times past,” says Dr. Bartlett. “Transplant programs have been very slow to understand the changing paradigm and the need to change their approach.”
In liver transplantation, Sandy Feng, MD, PhD, professor of surgery at the University of California, San Francisco, says outcomes may be more challenging and may deteriorate overall, because donor age is a significant risk factor. “The negative impact of increasing donor age on liver transplant outcomes is very stable,” she says. “There is a physiologic limitation to the quality of the organs that are imposed by increased age.”
She adds, “Unless we have some scientific approaches or research-based strategies to improve the function of lower quality, older organs, I think that increasing donor age is going to translate into inferior outcomes.”
Time for More Research
Dr. Feng, along with others at the American Society of Transplant Surgeons, is promoting innovative research on deceased donor organs, and specifically on donation after brain death. “This is an area where research has been fairly anemic because there are tremendous ethical, logistical and regulatory challenges,” she says. “What we envision is that you might be able to give something to the brain dead donors that will be favorable for organ well-being and will translate into improved posttransplant outcomes,” Dr. Feng says. “But you've got a lot of challenges, beginning with the donor family and consent, people on the waitlist and also the donor and recipient hospitals.”
“This is an example of the kind of study that would have potential to improve the quality of organs being used for transplant, particularly the lower quality organs that need improvement,” she adds. “It might allow us to use organs we currently don't use.”
Changing Patient Expectations
While an increase in ECD organs is the new reality, public perception and to some extent regulatory agencies' perceptions may lag behind the reality of the changed and changing donor pool, says Dr. Bartlett.
“I think we have to adapt and change the expectations of our patients,” Dr. Feng says. “Patients should be able to expect what is an average quality organ, but what is now average is changing because the entire donor pool is shifting.”
“There is always the tension between using a marginal organ which fails, and not using the organ, resulting in a patient death on the waiting list,” says Prof. Watson. “The difficulty is getting the public and media to accept this and support surgeons in taking risks for the population of patients as a whole.”
The Impact of Sequestration
The National Institutes of Health (NIH) has announced that sequestration, which was signed as an order by President Obama on March 1,2013, requires the NIH to cut 5%, or $1.55 billion, of its fiscal year 2013 budget.The cut must be applied evenly across all programs, projects and activities. Every area of medical research will be affected.
According to the NIH, approximately 700 fewer competitive research project grants will be issued. Additionally, about 750 fewer new patients will be admitted to the NIH Clinical Center and there will be no increase in stipends for National Research Service Award recipients in fiscal year 2013. The impact of sequestration, the NIH says, will delay medical progress and present a risk to the scientific workforce.
The adjusted NIH Institute and Center (IC) pay lines and funding strategies can be found on the NIH grants and funding website at: grants.nih.gov/grants/financial.
According to the NIH, reductions to non-competing research project grants vary depending on the circumstances of the particular IC, but the NIH-wide average is 4.7%. Additionally, the NIH says that the sequester does not stipulate the precise reduction to each scientific area. However, it is likely that most scientific areas will be reduced by about 5% because the sequester is being applied broadly at the NIH IC level.
In an American Society of Transplantation (AST) blog posted March 25, 2013 on the AST website, Roz Mannon, MD, president of the society, noted that for more than a decade, AST has worked closely with the U.S. Senate and House of Representatives Committees on Appropriations, supporting biomedical research, and continues to educate and remind politicians about the significant benefits of a strong NIH national biomedical research engine.
Additionally, the American Society of Transplant Surgeons (ASTS) advises Congress and related federal agencies on decisions that influence the practice and science of transplantation.
What Sequestration Means for Transplantation
According to a March 2013 Legislative and Regulatory Update sent via from the ASTS, sequestration's greatest impact for physicians, hospitals and other healthcare providers will be through the 2% cut in Medicare physician payments; cuts to the Department of Health and Human Services, the Centers for Disease Control and Prevention, the NIH, the Food and Drug Administration and other agencies with direct healthcare oversight; graduate medical education funding; and potential delay of efforts to move on a permanent fix to Medicare physician payments.
The ASTS further notes that the 2% percent cuts are not cumulative: “So, for the entire nine-year period 2013-2021, providers and plans will be paid 98 cents on the dollar; however, because Medicare costs are projected to rise from 2013 through 2021, the dollar amount saved by this 2% cut will increase, from $11 billion in 2013 to $11.4 billion in 2014 and, ultimately, to $17.8 billion in 2021. For 2014 through 2021, the Medicare cut will remain at 2% while the percentage [of] cuts in other programs will gradually shrink.”
Unless we have some scientific approaches or research-based strategies to improve the function of lower quality, older organs, I think that increasing donor age is going to translate into inferior outcomes.