Testimony Before the House Appropriations Committee on Funding for Transplant Research

Presented by J. Harold Helderman, M.D.

April 15, 1997

Date posted on the Web: April 23, 1997

Mr. Chairman and members of the subcommittee, thank you for the opportunity to present testimony on behalf of the American Society of Transplant Physicians (ASTP) concerning appropriations for the National Institutes of Health and in particular the NIAID, NIDDK, and NHLBI.

I am Hal Helderman, Professor of Medicine and Medical Director of Transplantation at Vanderbilt University, and more pertinent for this exercise, I am the President-Elect of the ASTP. Our organization, which has no governmental support, was established in 1982 and currently has a membership of over 1,000 physicians, surgeons, and scientists. The practices and careers of our members are focused in the broad field of transplantation medicine which spans the disciplines of cardiology, hepatology, nephrology, pulmonology, infectious disease, histocompatability as well as basic research in the field of immunobiology and transplantation. Interestingly, nearly 25% of our members are surgeons with expertise in the related surgical specialties of solid organ transplantation. The ASTP therefore represents the largest and broadest number of professionals in the field of transplantation in the United States. Our Society is committed to 3 basic principles:

• The providing of the best care to the greatest number of patients, with priority resting with the patient and not the individual transplant centers or physicians;
• Insuring equal access to the "gift of life" regardless of race, gender, or ability to pay; and
• The discovery of novels means to improve transplant outcomes based on sound scientific principles of immunobiology.

Over the last 20 years, transplantation of solid organs has moved from experimental to accepted therapy, with over 200,000 total transplants having been performed in the past 25 years, and nearly 20,000 transplants performed in 1996 alone. The success with this procedure has improved greatly over the years with now almost all solid organ recipients enjoying a 75-98% survival rate at one year. Realization of this improved survival for people with end stage organ failure has led to a tremendous increase in the number of patients placed on transplant waiting lists, increasing from 16,000 in 1988 to now over 51,000. This increase has been associated with a number of problems including increased waiting time for a transplant, which now ranges from 254 days for a liver, to 832 days for a kidney. Unfortunately heart, liver and lung failure are progressive diseases with no current dialysis equivalent to support patients, and many die while waiting for a life saving transplant. Deaths of patients on the list has increased from 2,889 in 1993 to over 3,500 patients in 1996, nearly 10 patients a day.

The overwhelming limitation to being able to offer this life saving procedure to more patients is the shortage of available donors and the disparity between supply of available donors and the patients in need continue to worsen. Many individuals and organizations are working on this problem, but there is no national or governmental policy or program to spearhead this effort. Each year our organization has identified the shortage of available donors as the number one problem in the field of transplantation, but minimal progress has been made. We seek more funds for investment in the Division of Transplantation of HRSA to enhance organ donor awareness and improve public trust in the process, as family refusal is still the number one cause of loss of potential donors today, amounting to over 40% of identified donors.

We strongly believe that research in transplantation leads to solutions that save lives. There are several research areas which are of importance to all disciplines of solid organ transplantation, and few that are unique to the individual organ transplanted. As one of the founding societies of the Council of American Kidney Societies (CAKS) the umbrella organization bringing together those groups with common goals of maximizing treatment, preventing, and performing research into kidney disease. We strongly endorse CAKS recommendations on kidney-oriented research in general and kidney transplantation in particular. We strongly support the recommendation that NIDDK receive a %9 increase, from $833.8 million to $90.9 million. The ASTP supports the request for $13.9 billion for NIH for the FY98. CAKS and our sister member societies will be providing your committee the detailed rationale and research agenda for kidney-oriented issues. The ASTP has a broader purview in transplantation of the range of solid organs including kidney. In the remainder of my testimony, I would like to provide a basic outline in clinical and basic science research.

CLINICAL

1. End stage organ failure databases are needed for every organ, like the ESRD database that now exists for renal failure. These databases could help to be better understand and plan the needs for transplantation and examine therapies that could alter the natural history of end stage disease. End stage heart failure for example is the number one admitting volume diagnosis (number of admissions X length of stay) in the Medicare system and has the highest readmission rate. There are an estimated one million people with this diagnosis which has as much or more of an impact on the health care budget as any other disease. In addition, the increasing average age of the population indicates that this disease will only increase. Funds need to be directed to each Institute at the NIH to develop these databases.
2. Clinical trials on new immunosuppressive agents. There has been a plateau in the improvement in survival with transplantation and no one agent can be used alone due to unacceptable toxicity or side effects. New agents will soon be ready for clinical trials and money needs to be directed to support these studies. To date there have been no clinical trials and in this area sponsored by the NIH except in renal transplant recipients and we need to study the impact of these new agents on pediatric as well as adult patients. The ultimate goal is to design strategies that will allow the use of minimal if any immunosupressive medication by inducing tolerance to the transplanted organ by the recipient.
3. Clinical trials to assess the benefit of transplantation. There have been few good multicenter clinical trials to prove the comparative benefit of transplantation in terms of outcome or quality of life. A good example is in the area of diabetes, which is the leading indication for cadaver kidney transplant. Great progress has been made in the filed of pancreas transplantation and now simultaneous kidney/pancreas transplant offers greater survival at five years than kidney alone, and the majority of patients no longer need insulin. However this combined transplant is not covered by most insurance companies because definitive prospective studies have not been conducted. The NIH needs to sponsor a trial to document the superior benefit of combined kidney/pancreas transplant to convince third party payers and Medicare to cover this procedure, and further fund research to assess the comparative benefit of whole organ (pancreas) versus islet cell transplantation.

I would now like to discuss areas of basic science research in transplantation that deserve your attention.

BASIC SCIENCE

1. Chronic rejection. For most solid organs transplanted, chronic rejection continues to be the major cause of long term graft loss. It results in a progressive obliteration of the blood flow to the organ from subclinical rejection and other causes. This has remained the top priority in research in the past five years, and yet not enough funds have been devoted to this area to solve the problem. This is a growing problem as improved survival of patients with first kidney grafts has made retransplantation the leading indication for kidney transplant today, but many patients such as heart transplant recipients are not offered a retransplant due to the number of patients awaiting a first graft. New approaches are being examined including gene therapy to alter the function of the vessel wall cells to reverse injury induced by brain death and preservation as well as immune mechanisms. One new clinical advance is the development of an intravascular ultrasound imaging technique that allows measurement and detection of thickening of the vessel wall of the transplanted organ and follow changes over time. This is currently being performed in heart transplant recipients but the test is not being reimbursed. This is a perfect opportunity to have the NIH partner with industry to conduct a trial of new therapies to retard or prevent the development of this disease and combine the efforts of the basic scientist and clinician to understand the mechanisms that underlie chronic graft loss.
2. Tolerance. As noted earlier, the ultimate goal in transplantation is development of tolerance, or freedom from the need for immunosuppressive drugs to prevent rejection. Many new approaches are being investigated and this remains one of the top research priorities in our field. More funds need to be focused in this critical area of research which will allow the elimination of drug related side effects.
3. Xenotransplanation. The increasing disparity between the number of patients listed for transplant and the number of available donors leads to an increasing number of patients dying on the waiting list. Use of organs and tissues from non-primate animals could provide an immediate resource alternative for patients with critical need for a life saving transplant. The NIH needs increased funding to support this important area of exploration. We must learn the immunologic barriers in xenotransplant, strategies to overcome these barriers and safeguards with respect to the possibility of xeno infections that might be introduced into man.
4. Brain death: This is an area of significant importance that has not received much funding support in the past. Brain death causes variable degrees of ischemic injury to all organs of the body, but irreversible injury is currently difficult to diagnose. Severe ischemia may cause early nonfunction of the graft after transplant, a problem which is highly correlated with acute and long term graft loss. Only 40% of all kidney donors become heart donors because of unexplained injury to the heart likely due to ischemia. Research in this area directed at preventing the injury associated with brain death could double the number of available hearts and maximize the function of the limited number of organs identified.

I have tried to outline for you some of the major areas of clinical and basic science research in extra renal organ transplantation that need increased funding to help solve the problems associated with transplantation. Although expensive, transplantation is cost effective, and may be the only hope for not just improved survival for many patients, but a chance to help raise their families and return to gainful employment. The ASTP believes that we are on the threshold of many important advances in our understanding of the problems posed by the transplantation of organs, and research is critical to making this option available to more people. The field of transplantation is the perfect example of an ideal interaction between the clinician and the basic scientist, as they collectively try to unravel the mysteries of the immune system and apply that knowledge to improving the lives of thousands of patients with end stage renal disease. I hope that you will agree with the need for increasing funding for the NIH and the Division of Transplantation at HRSA, in these areas. There can be few areas with more visible, truly life saving dividends than money invested in research in the field of transplantation. Thank you again for this opportunity to testify before your committee.

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