Saturday, February 24, 2007

Kidney Allocation and Age

UNOS held a public forum on proposed changes to the kidney allocation system on February 8, 2007, in Dallas. For those who didn't attend, the slides presented at the meeting are available, as well as a more understandable but narrowly-focused summary from the PKD Foundation. Approximately 200 people attended in person and an additional 150 attended by web conference or phone, and they had a lot to talk about.

The proposed change that has been focused on the most is incorporating age into the allocation system. To be specific, the changes would incorporate the age of adult candidates as one factor in prioritizing the allocation of standard criteria donor (SCD) kidneys. All of those qualifiers are important, since reading most accounts could lead people to believe:

  • that older age doesn't currently play a factor in candidacy for transplantation (it does, in evaluating and deciding to list patients for transplant),
  • that younger age isn't currently used in the allocation system (it is, in that children are given extra "points" in the current system),
  • that all kidneys available will be allocated through this system (they won't, since expanded criteria donor [ECD] kidneys will be allocated purely on waiting time), or
  • that age will be the only factor used in allocation (it won't be, it will be one of many factors).

The current system strives to be as fair as possible. Fairness coexists with utility, which depends on "matching" donors and recipients into combinations most likely to have the best outcomes. Over the years, the importance of "matching" based on HLA antigens has decreased, but the logic of matching based on age is still solid. A 25-year-old kidney in a 75-year-old patient is likely to outlive its recipient, still having years of potential function when the recipient dies of other causes. The current system has no way to account for this form of "matching." Kidneys from donors over the age of 60 are considered expanded criteria donor (ECD) kidneys, as well as those from donors over the age of 50 with less-than-ideal conditions. While these kidneys may be less likely to last for decades than standard critera donor (SCD) kidneys, older recipients are also often less likely to live as long, which lessens the chance that donated kidneys will outlive their recipients. ECD kidneys will still be allocated primarily by waiting time, so older recipients will still be able to receive kidneys based on their waiting time, kidneys that could likely work well for them.

Most of the news coverage of this story seems to be from Chicago, starting with an article in the Chicago Tribune the morning after the public forum. The article is clear and reasonably balanced, though a bit opposed. Two patients with polycystic kidney disease were interviewed for the article--Jack Fassnacht wondering if the new proposal is "suggesting the life of a 30-something has more value than the life of a 50-something" and Norma Knowles asking ""Who's to say an older person's five years of life are any less important than a younger person's nine years?" Both of these are impossible questions to answer, and the new proposal is NOT attempting to answer them. It measures each additional year of adult life as equal, whether your 20th, 50th, or 80th, basing its priority on whether one is likely to see that year. Some are wondering whether UNOS is valuing one person's 30th year over another's 70th year, which is dicey, but the converse of valuing one person's 70th year over another's 30th year is even less justifiable.

These issues were more recently tackled in a Chicago Sun-Times column by Sue Ontiveros. She presents a much firmer defense of the advantages of the current system and those advantaged by it. She argues:

  • that "the person who most needs a new kidney is selected first" (unlikely, since there are no measures of "need" or medical urgency in the current system),
  • that a new system could later incorporate gender or race (these factors have been analyzed and excluded), and
  • that "no one has said that the current criteria for choosing kidney transplant recipients isn't working." (very unlikely, since someone is always saying that the current criteria aren't working!).

Most flabbergasting to me is that she argues that the proposed change is "telling people it pays to be young and ill" and not "rewarding" her for maintaining the function of her native kidneys. First, I don't know of anyone with kidney disease who would think "hey, if my kidneys fail sooner, I'll have a better chance of getting a new one!" Accusations of personal responsibility cut both ways, when those that have congenital or immunologic diseases consider diabetes and hypertension to be purely the result of lifestyle. I think it's fairer to say that end-stage organ failure is a crisis under any circumstances. Second, native kidney function is far better than living with a transplant, so the reward that Ms. Ontiveros gets for her good habits is better health today, which I'm sure that anyone on the transplant list would be extremely envious of.

Ultimately, this debate makes some people angry, but it makes me rather sad. I may feel that transplanting a 20-year-old is a better use of a kidney than giving it to a 80-year-old, but could I look an 80-year-old in the eye and tell them that they don't "deserve" a kidney? That's much harder. UNOS has calculated that the proposed changes will result in an additional 11,457 years of life from kidney transplants than the current system. This is an impressive statistic, but what it tells me is that at least 11,457 years of life are lost to kidney disease, and probably far more than that. The supply of donor organs is extremely limited, and any improved system will still face this incredible shortfall and the faces of those who could benefit from transplantation but haven't had the chance to.


Saturday, February 17, 2007

Politicians and Transplantation

Politics is as much a part of transplantation as it is of any other part of life, transplant is arguably the most politicized and regulated field of medicine, and politicians have played many roles in the history of transplantation.

The most obvious role is that of transplant recipient. Like thousands of their constituents, several politicians have faced the seriousness of end-stage organ failure and experienced organ transplantation firsthand. The first politician to receive a transplant (that I know of) was Kansas City Mayor John Reardon, who received a heart transplant in February 1987. The next prominent example was Pennsylvania Governor Robert Casey, who received a heart-liver transplant for amyloidosis in June 1993. More recently, Texas state Senator Mario Gallegos (D, Houston) received a liver transplant last month for alcoholic cirrhosis. Questions of preferential treatment were raised when both of these politicians received their transplants surprisingly soon after being listed, but no evidence of favoritism was found, though Governor Casey's case led to changes in the allocation rules for those waiting for multiple lifesaving organs. Representative Charles Norwood (R, GA) unfortunately died of cancer this past week, having received a single lung transplant for idiopathic pulmonary fibrosis in October 2004. In Canada, Quebec finance minister Michel Audet received a heart transplant in 1992 and retired a few days ago on Valentine's Day. There may be more transplant recipients who are politicians that I've missed (feel free to leave comments), and the overall number isn't huge given the number of politicians. But at least some of those making laws and running the government do so with the perspective of a transplant patient.

Fewer transplant professionals have been politicians, since doing so means choosing to change careers, an entirely different decision than choosing to treat a serious illness. The only one I'm aware of is Senator Bill Frist (R, TN) who was a heart and heart-lung transplant surgeon at Vanderbilt University Medical Center before being elected to the Senate in 1994, and intends to return to medical practice since his term ended in 2006.

Finally, even without firsthand experience, many politicians have played major roles in the development of transplantation in the United States. Transplantation greatly expanded in the early 1980s with the development of cyclosporine--kidney transplant success rates went from 50% to 80-90% at one year, and liver, heart, and lung transplants first reached viable success rates and wide application in these years. Increased success and increased application led to dramatically increased demand, which until that time had been met by smaller, local systems with few uniform processes and little sharing across geographical areas. In response to a number of pleas for donor organs, many directed to him, President Ronald Reagan [1][2][3][4][5] directed Congress to devise a system for organ allocation in the United States, which took shape in the National Organ Transplant Act of 1984, written by then-Congressman Al Gore. The development and implementation of the Act reflected tension between the Republican administration and the Democratic congress, ultimately resulting in the government not taking control of organ allocation, but assigning the responsibility to a private contractor: UNOS.

By the late 1990s, transplantation had expanded futher and the disparities in organ allocation between different regions of the country had become even wider, which led Secretary of Health and Human Services Donna Shalala to propose changes to the system that would require sharing across regional boundaries and give organs preferentially to the sickest patients first rather than those who had been waiting the longest. Like the National Organ Transplant Act of 15 years before, this legislation provoked controversy as smaller units (transplant centers and states) feared giving up control to larger ones, and private organizations such as UNOS were wary of increased governmental control. The tables were slightly reversed at this point, with a Democratic administration and Republican congress, which allowed this stronger legislation to pass in the form of the 2000 Final Rule.

They've been under attack in transplantation, like in every other part of society, but the influence of politicians has seemed to make things better for the transplant community. Unfortunately, there are many problems that still remain to be solved, so hopefully politicians of the future will have the interest and fortitude to tackle them. And we haven't had a transplanted president...yet.


Saturday, February 10, 2007

Transplant Pathology

I had another biopsy last weekend. It's become a familiar routine of 6 AM departures, four hours bedrest, and waiting for a phone call in the evening with results. The details vary by organ, by institution, and by patient, but biopsies are a part of life for almost everyone involved in transplantation.

Biopsy samples, of course, go to pathology, and the development of transplant pathology is one of the more interesting spinoffs in the history of transplants and of pathology. Rejection was identified in early laboratory research in transplantation, and characterizing rejection pathologically led to several important insights into transplantation. In this way, pathology played a role similar to pharmacology, as the identification and development of immunosuppressant drugs helped show exactly what was needed for transplantation to be a success. However, from the pathology standpoint, transplantation isn't a "natural" condition like cancer--it has similarities to autoimmunity, but pathologists had to identify and diagnose rejection and other problems with transplanted organs only after surgeons and other clinicians began transplanting organs. Even if the role of pathologists wasn't thought of initially, they willingly came along for the ride, and certainly got to work in developing the field.

Transplant pathology is fairly standardized, and much of this standardization started from the Banff conferences. These began as meetings to reach a consensus on what characterized kidney transplant rejection, later weaving in the NIH-CCTT (Cooperative Clinical Trials in Transplantation) guidelines, and expanding to describe rejection of the pancreas and liver. The ISHLT (International Society of Heart and Lung Transplantation) took a similar lead in characterizing heart and lung transplant rejection. Having these standards is invaluable for the transplant world to communicate clearly about rejection (diagnosing and treating it) when many individuals may focus more on an organ or organ system rather than transplantation itself. Many of these standards, and all sorts of other information, can be found at the TPIS (Transplant Pathology Internet Services) site.

It hasn't stopped there, though. One purpose of making the early systems was to have a standard way to describe rejection for clinical studies, but thanks to these clinical studies, serious acute rejection and graft loss aren't nearly as common as it once was. So pathologists have worked on developing new ways of characterizing rejection and organ function to serve as "surrogate endpoints" to identify more subtle issues in transplant function. These have successively incorporated the latest techniques in biology, such as cytokine profiles, DNA microarrays, and genomics and proteomics. They have also helped describe problems such as acute humoral rejection (by C4d staining) and infections (such as BK virus) that wouldn't be nearly as well-understood without pathology input.

My biopsy turned out fine--recovered quickly, got the results, no huge surprises, a few changes in treatment, but still some unanswered questions. For now, transplant pathology can recede in my mind, but I'm sure the field will continue to develop and will be there the next time I need them.


Saturday, February 3, 2007

USC Liver Transplant

Hearing that a transplant program has unexpectedly low graft or patient survival rates brings the assumption that the program's staff must be unqualified or inexperienced (not doing enough), or uncaring or incompetent (not trying hard enough). But what if the problem is actually that they're doing too much and trying too hard?

At the end of the year, the Los Angeles Times reported on the unexpectedly high death rate of patients in the liver transplant program at the University of Southern California (USC). They told the stories of several individual patients who were extremely sick, who would likely die with or without a liver transplant, who may have received marginal donor organs, but ultimately were transplanted at USC when other programs had turned them down. The available data support the notion that USC has a very high-risk patient population: the "expected" survival rate for USC was lower than the national average, and USC patients had a higher risk of dying before a transplant, not just afterwards. There were also systems problems within the program, as detailed both by the LA Times and the USC Daily Trojan student newspaper--these should be corrected, and plans to do so are in place. But the USC dilemma generates the more vexing question of who is an appropriate transplant candidate and who is "too sick" to receive a treatment designed for "end-stage" presumably fatal disease.

Much of the response to this story was defensive, with letters to the editor in defense of both the field of liver transplantation and the USC program in particular. For a field founded on treating otherwise untreatable diseases, and that has made untreatable diseases treatable, this defense is perfectly understandable. Also, the line between acceptable and untenable transplant candidates is a moving target that has generally become more permissive over time. Personally, I can't imagine the despair of being "too sick to transplant" and can fully understand why patients would seek out any program that would offer them a chance, and why a program would strive to give them that chance.

Yet the fact remains that the outcomes of patients treated at USC are poor by national standards, and as insightfully stated by Dr. David Mulligan, chairman of transplant surgery at Mayo Clinic Hospital in Phoenix: "They're pushing it as hard as they can and having the results that you'd expect to see." Beyond the "push" for individual patients, though, is a "push" on much larger systems:

  • The staff is devoting its considerable training and talents to some patients who stand little chance of benefitting from them.
  • USC is dedicating resources to a program that may ultimately harm it more than help it as an institution.
  • Organizations such as OneLegacy (the organ procurement organization serving Southern California) and UNOS are spending their time and energy matching donors and recipients who may have very little chance of success.
  • Medicare, Medicaid, or private insurers are paying for an expensive treatment that has less chance of succeeding than it may under more normal circumstances.

The follow-up to this story indicates that, however good the intentions of USC's previous practices, they are changing. It will take time to see if these changes improve their survival rates and repair their reputation. But the patients who are too sick to transplant are still out there, and someday treating them successfully is a challenge to the field of transplantation and medicine in general.