EVEN MORE HOPE !

An earlier post on June 19, 2013 delved deeply into the rationale behind the HOPE Legislation currently in the U.S. Congress to permit cautious exploration of the use of HIV +ve donor organs for transplantation into HIV +ve recipients, along with appropriate observational research. At that time the Senate had unanimously passed the bill but the House of Representatives was just beginning to take action.Now there is good news that on 7/17/13 the Energy and Commerce Committee of the House of Representative also voted unanimously to pass H.R. 698. Additional co-sponsors have also signed on to Representative Lois Capps’ bill – now at a total of 51 (12% of the 435 Representatives). Now we await action from the entire House of Representatives.

This legislation is an important bipartisan effort, supported by multiple medical, patient and social organizations because it represents a potential win-win for everyone. Expansion of the organ donor pool, carefully supervised clinical research with informed consent of the participating subjects, oversight by the government, support of the major transplant organizations, potential reduction of transplant candidate deaths, etc.

Keep tuned to this blog for updates as additional steps happen. It is beginning to look like this legislative action may become real in the not too distant future.

TRANSPLANT JARGON EXPLAINED

    A GLOSSARY OF TRANSPLANT TERMINOLOGY

    • allocation – algorithm for distribution of a deceased donor organ
    • allograft – a donor organ from a non-identical member of the same species (e.g., parent to child)
    • autograft – a donor organ from a genetically identical member of the same species (e.g., between clones or identical twins)
    • cold ischemia – time between cessation of blood flow to the donor organ and restoration of blood flow during transplantation
    • en bloc – organs that remain anatomically connected (e.g., 2 pediatric kidneys still attached to the aorta and vena cava)
    • DCD – Donor after Circulatory Death is a deceased organ donor whose death was declared based on cessation of cardiac activity
    • deceased donor – a human being whose organs have been removed after death for the purpose of transplantation
    • delayed graft function (DGF) – a newly transplanted organ that is alive (receiving blood flow) but has not yet begun to function (e.g., a transplanted kidney that is not yet making urine)
    • donor service area (DSA) – the geographic region that is the smallest unit of organ allocation and is served by one OPO
    • EPTS (estimated post transplant survival) – a formula based on four medical factors about the transplant candidate (age, time on dialysis, presence of diabetes, history of a prior transplant) that determines the statistical likelihood of survival of a patient in comparison to other patients 
    • expanded criteria donor (ECD) – a deceased organ donor who meets the UNOS definition of a less than optimal donor because of age, cause of death or medical history. In general, these organs are more vulnerable to all types of transplant related injury than standard criteria organs.
    • graft – organ +/- tissue that is transplanted
    • KDPI – kidney donor profile index is a numerical measure that combines ten dimensions of information about a donor, including clinical information and demographics, to express the quality of the donor kidney relative to other donors.(optn KDPI source info). Ranging from 1-100%, a value of 75% means that this kidney has a relative risk of failing that is higher than 75% of deceased donor kidneys.
    • immunosuppression – pharmacologic or biologic therapy administered to diminish the strength of the response of the immune system
    • import – an organ that has been recovered in a different UNOS region or DSA and transported in to the transplant center and patient. Importanting an organ prolongs the cold ischemia period.
    • LYFT (life years from transplant) – the statistical quality adjusted survival benefit provided by the transplantation of a given organ to a given recipient
    • multi-visceral – a transplant in which more than one abdominal organ is transplanted, usually involving the liver +/- pancreas, duodenum, stomach, small intestine
    • NOTA (National Organ Transplant Act) – federal legislation, P.L. 98-507,  enacted in 1984 to address the organ donation shortage and to improve organ matching and placement. The act and its amendments establish the national registry for organ matching and call for a transplant network to be operated by a non-profit organization under federal contract.
    • opo (organ procurement organization) – a private, non-profit organization responsible for increasing donor registration in the assigned donor service area and for coordinating the donation process in the service area hospitals.
    • OPTN (organ procurement and transplantation network) – established by the U.S. congress when it enacted the National Organ Transplant Act (NOTA), this is a unified transplant network to be operated by a private, non-profit organization under federal contract.
    • rejection – recognition and attack of the transplanted organ and tissue by the host’s immune system
    • standard criteria donor (SCD) – a deceased organ donor who does not meet the UNOS definition of an expanded criteria donor. In general, these organs are most likely to function promptly after transplantation, and most likely to continue functioning for may years.
    • SRTR  (Scientific Registry of Transplant Recipients) – the primary source of transplant data in the U.S., containing information from 1988 and later. These data are developed from mandatory transplant center reports and are used by multiple regulatory agencies and researchers.
    • tolerance – a host’s immune system’s failure to recognize and respond to a specific donor’s organ (or other stimulus) while retaining all other functions
    • Thrombosis – the condition of blood clot blocking flow through a blood vessel
    • UNOS (United Network for Organ Sharing) – the private, non-profit organization that manages the nation’s organ transplant system under contract with the federal government.
    • VCA (vascularized composite allograft) -multiple tissues such as muscle, bone, nerve and skin that are transplanted as a functional unit and require the surgical attachment of blood vessels (e.g., a hand or face).
    • xenograft – a donor organ from a member of a different species (e.g., pig to human)

    If you don’t see the term you were seeking, please ask for an explanation by submitting a COMMENT.

      AMERICAN LEGISLATORS SLOWLY JOINING THE IMMUNOSUPPRESSIVE DRUG COVERAGE EFFORT

      U.S. congressional efforts are slowly in process, seeking to close the ridiculous catch-22 that ensnares kidney transplant recipients 36 months after transplantation. This bureaucratic trap halts Medicare coverage of their expensive immunosuppressive medications but resumes payment for dialysis when the resulting rejection causes the kidney to fail. In two prior postings on this blog; March 7, 2013 and  May 27, 2013 status reports on the Senate and House versions of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2013 were provided.

      Today’s report is that additional co-sponsors have “signed on” to each bill. The Senate bill, initially introduced by Senator Durbin from Illinois, now has 11 co-sponsors. This means that 12/100 Senators, or 12% have committed to supporting the bill. Another 88 to go! Are your Senators on board? Use this Senate link to check whether both of your Senators have “signed on”. If they have not, please give them a phone call……or send them an e-mail. Ask them to sign on to S.323 (the formal # for this bill in the Senate).

      The current status in the House of Representatives is that 67 members have “signed on” to co-sponsor Representative Michael Burgess’ original bill. This makes a total of 68/435, or 16% who have committed to supporting the bill.   Use this House link to determine whether your Representative is on the list and, if not, contact him/her. Ask for support of H.R. 1428.

      Together we can make a difference. Legislators DO respond to their constituents. If we make it very clear that this Catch-22 is unacceptable, that we insist on change, and that we hold our own politicians accountable, we can be the agents of change. Take a few moments to take the simple steps outlined above. And, pass the link for this blog to someone else who will help make the change. We do have this power. You have this power. Please use it.

      FACE + HAND TRANSPLANTS : NEW NAME, NEW REGULATORY NICHE

      Clinical transplantation has moved forward in leaps and bounds, surpassing the speed of the U.S.  government in addressing regulatory standards for new transplant types. This is neither an irrelevant nor a minor issue and has just been definitively addressed by the Final Rule published in the July 3, 2013 Federal Register. The National Organ Transplant Act (NOTA) originally enacted in 1984 had defined a specific list of transplant organs based on all of the transplant types that were performed in that era. The Organ Procurement and Transplantation Network (OPTN) and United Network for Organ Sharing (UNOS) oversee and regulate those types of organ transplantation with a fully developed set of bylaws for member institutions and policies that determine how transplants are undertaken. These transplants currently include:

      ORGAN TRANSPLANTS
      Kidney
      Liver
      Heart
      Lung
      Pancreas
      Intestine (any part of the intestinal tract)

      In contrast, human cells or tissue for transplantation are under the regulatory jurisdiction of the Food and Drug Administration (FDA) under Section 361 of the Public Health Service Act and 21 CFR parts 1270 and 1271.  Examples (not inclusive) of Cell and Tissue “Implants/Transplants” include:

      CELL + TISSUE “IMPLANTS/TRANSPLANTS” 
      Bone
      Skin
      Cornea
      Ligaments
      Stem cells
      Peripheral blood
      Cord blood
      Oocytes
      Semen

      Face, hand, larynx, and abdominal wall transplants are all examples of transplants that did not clearly fit into either of the two pre-existing categories. Agreeing with advocates within the transplant community, the Secretary of Health and Human Services issued this Final Rule that has formally created a new category of Vascularized Composite Allografts (VCA), (allograft = transplant between non-identical members of the same species) that is defined based on functions below (ischemia is a period of interrupted blood, see below):

      VASCULARIZED COMPOSITE ALLOGRAFTS 

      1. Vascularized – requires blood flow by surgical connection
      2. Contains multiple tissue types
      3. Recovered from a human donor as an anatomical/structural unit
      4. Transplanted into a human recipient as an anatomical/structural unit
      5. Minimally manipulated or processed (but may be cut or shaped)
      6. For homologous use (i.e., to be used for the same purpose in the recipient as it was in the donor)
      7. Subject to ischemia and therefore stored only temporarily
      8. Subject to allograft rejection and generally requiring immunosuppression

      The Final Rule also clearly stipulates that VCA transplants fall under the jurisdiction of the OPTN/UNOS, not the FDA. Major implications of this definition are that VCA transplants may only be performed at OPTN member institutions in good standing. New policies specifically applicable to VCA transplants clearly need to be developed by the OPTN/UNOS.

      Because of the unique issues pertaining to donor consent for these specific transplant types, wherein donor identification may be retained (e.g., fingerprints and facial identifiers), the Final Rule implies that donor specific consent should be undertaken on a case-by-case basis. This is the current ad hoc practice. But new issues of allocation will arise if the number of transplants begins to grow substantially. For example, there is no other transplant type in which skin color may be relevant!

      Overall, a new field of medicine is currently developing at a very rapid pace. This one step is an important one. It will be challenging and exciting as others are made. Stay tuned.

      KIDNEY TRIAGE BECOMING MORE SEVERE

      Acknowledging reality, the Board of Directors of the United Network for Organ Sharing (UNOS)  accepted recommended changes to the allocation policy for deceased donor kidneys throughout the U.S. at its meeting on June 24-25, 2013. This policy determines how a specific kidney is offered to a specific waiting patient by defining how the UNOS computer generates the specific list in response to availability of a donor.  In the context of the extraordinary discrepancy between people waiting and the number of organs available, several fundamental problems are intended to be improved with the amended policy (see below).

      A key change involves implementation of the Kidney Donor Profile Index (KDPI) as a measure of the risk of kidney failure after transplantation, with 100% being the worst and 1% the best possible values. An organ with a KDPI of 20% is more likely to function than 80% of transplanted kidneys – pretty darned good. Since one would not like to transplant an organ that is likely to fail, the KDPI is used as a direct measure of donor kidney quality.

      Waiting candidates are stratified into 4 groups based on the KDPI and a second formula, the estimated post-transplant survival (EPTS).  This not-so-subtle means of including the candidate’s statistical life expectancy following transplantation is a major step in the allocation scheme, taken in order to maximize the number of life years for the kidney following transplantation (LYFT).  It is based on the candidate age, length of time on dialysis, prior transplantation and presence of diabetes. However, the new policy amendment will incorporate the EPTS to advantage just those 20% of candidates with the best likely survival.

      Now, combining the KDPI and EPTS will lead to the 20% of best KDPI organs being matched to pediatric patients and adult patients with the best EPTS. Pediatric patients are still given an advantage for organs with a KDPI up to 35%. Between KDPI of 35-85% adult recipients are addressed by the standard allocation factors already in effect. Above 85% broad sharing (beyond local areas) will be undertaken promptly in order to avoid discarding potentially transplantable organs.

      These changes have been neither reactive nor rapid, but have followed years of debate and formal procedure that included opportunities for input from all stakeholders. Nonetheless, the starkness of  including some healthier candidates while excluding sicker ones from access to the best kidneys, is not lost on anyone involved. This “cherry-picking” of transplant candidates is a deeply distasteful but necessary response to the lack of sufficient resources. Please take a moment to register your opinion about these changes by answering the poll at the bottom right of this webpage – thanks.