Dying to Live is an hour-long documentary produced and directed by John Robbins and Lance Lipman. It follows the lives of patients and donors involved in organ transplants, all of them at Piedmont Hospital in Atlanta. The title is a bit of a misnomer. Of the two donors featured, one is actually a live kidney donor who has no complications after her surgery.

The one kidney patient in the documentary, Andrew Persaud, is a re-insurance broker who has been on hemodialysis for several months. He wants to get a transplant as soon as possible. Rather than wait for a deceased donor, he conducts a search for a live donor. He has created a website AndrewNeedsAKidney to describe his situation and promote in his search. Barbara Kilgore, a teaching nurse at Emory Adventist Hospital does not know Andrew, but hears about his condition from her daughter, who is a friend of Andrew’s sister. Ms. Kilgore volunteers to get tested. She is a match and a few months later she becomes a living donor for Mr. Persaud.

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Andrew Persaud and Barbara Kilgore. Video still from Dying to Live

The other three patients featured in the movie are on the liver waiting list. Their experience is much more desperate than that of Mr. Persaud. As mentioned in many previous blog posts, patients with end-stage kidney disease (ESRD), can be kept alive mechanically through dialysis. Since kidney patients can survive several years on dialysis, the distribution of organs is weighted mostly by time on the list and difficulty of finding a match.

The situation is quite different for liver patients. There is no mechanical therapy available for liver failure. The only treatment is transplant. There is also a severe shortage of transplantable livers. Thus, rather than distributing livers based on how long a patient has been waiting, they are distributed to the sickest patients first. The United Network for Organ Sharing (UNOS) uses a measure called the MELD score (model for end-stage liver disease) to prioritize patients who are likely to die soon without an immediate transplant.

In a poignant scene shot during a transplant support group meeting sponsored by Piedmont Hospital, a patient candidly talks about his desire to get sicker faster so that he can move to the top of the waiting list and get a transplant sooner (or die sooner if an organ isn’t found).

One of the liver patients is Kevin Ferwerda. His condition is serious and his health is declining. He has been on the waiting list for several years but he is not yet near death, so does not qualify for an immediate transplant. Instead, he continues to wait while he struggles with recurring blockage of his bile duct that results in serious infections that require frequent hospital stays. When he is sick, his MELD score goes up and he moves up the list. As the doctors treat him, he gets better, and he moves down the list. This cycle puts a lot of stress on him both medically and emotionally. You can see and hear the tension as he and his wife Alyson discuss their life together raising three young children.

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Kevin and Alyson Ferwerda. Video still from Dying to Live

Because of the large number of family members and friends interviewed, it is often hard to keep track of which story goes with which patient. But overall the movie does an excellent job of describing the ups and downs experienced by everyone who is waiting and hoping for an organ or agonizing over the death of a loved one. The film also does a good job of confronting and dispelling some common misconceptions family members have about consenting to organ donation. The movie made its debut at the Hawaii International Film Festival in 2010 and later that year won an award at the Los Angeles Film Festival.

Note: Dying To Live is available for $248 at the Icarus Films website, a price that includes public performance and broadcast rights. However, if you contact the firm via email, you can purchase a copy of the film for individual use for $39 plus shipping. Unfortunately, this movie isn’t available for sale at Amazon or for rent on Netflix.

[Update: The tool developed by Arbor Research described in this blog post is no longer available.]

If you are a kidney patient considering transplant as a therapy option, you are probably wondering how long you can expect to wait for a deceased donor transplant. There is a free online tool available that you can use to estimate the typical wait time. The tool, developed by Arbor Research, asks four simple questions,

  1. Which transplant center are you a patient at
  2. What is your blood type
  3. Are you a juvenile or an adult
  4. If you are an adult, will you (actually your transplant surgeon) accept an expanded criteria donor (ECD)

The tool is fast and easy to use. However, if you have high sensitivity to human leukocyte antigens, then be aware that the estimates will be too low for you, as I explain later.

About the data

The calculator website doesn’t provide any documentation on how it works and what data was used. Luckily, I was able to get detailed information from Arbor Research. Much thanks to Melissa Fava, a coordinator, and Keith McCullough, a data analyst, both at Arbor Research, for taking time to answer all my questions and explaining upcoming updates to the tool.

The typical wait time is the median time to transplant among those who received a transplant in 2008 or 2009. The calculator uses patient data from the Scientific Registry of Transplant Recipients (SRTR) available as of October 2010. Only ‘kidney-alone’ transplant data was used, meaning data for kidney-pancreas, kidney-liver, or other multi-organ transplants were excluded. Transplants using organs from donors who test positive or indeterminate for hepatitis B or hepatitis C were excluded. For all transplant patients, the year they were added to the waiting list was found and the wait time calculated using mid-year convention.

Each transplant was grouped by transplant center, the recipient blood type (O, A, B, or AB), and the donor criteria a candidate is listed for (adult, standard criteria; adult, expanded criteria; or juvenile, standard criteria). The median wait times among recipients within each cell was reported. Cells with fewer than 10 subjects were not reported.

Why do wait times vary among transplant centers?

The typical wait time for a deceased donor kidney varies considerably from one transplant center to another. However, it isn’t because some centers are better at finding kidneys than others. Instead, it is based on three factors.

First, transplant centers generally don’t recover their own organs. Instead, they rely on an organ procurement organization (OPO) that recovers organs from a specific geographic region. Most OPOs serve more than one transplant center and have protocols in place to distribute the organs fairly among all the transplant centers within their donation service area (DSA).

Organ recovery rates vary considerable geographically. Recovery rates are lower in large cities. So OPOs that have a large proportion of their population in urban areas have the longest waiting lists. For instance, there are four separate OPOs in California and all contain at least one large city in their DSA. Thus, they all experience low organ donation recovery rates and all transplant centers in California have long wait times.

Second, within a single DSA, children’s hospitals have a shorter wait time than other hospitals. That’s because pediatric patients get priority access to organs.

Finally, some patients are easier to match than others. Patients with AB blood type can accept a donor organ of any other blood type. Patients with O blood type can only accept a donor organ from type O. Some patients have developed antibodies to human leukocyte antigens (HLAs) making it harder to find a matching kidney for them. Some transplant centers have more of these hard-to-match patients than others. So even though the organs are distributed fairly, some hospitals will have patients who end up waiting longer than others. As far as I am aware, transplant centers do not reject patients because they are hard to match or specialize in treating patients who are hard-to-match. The exception is transplant centers that offer intravenous immunoglobulin therapy to remove HLA antibodies prior to transplant.

National, regional, and transplant center median wait times

Let’s take a look at the data. The table below shows the typical wait times for all patients at all transplant centers combined. In general, patients with AB blood type are the quickest to find a match while O and B are the slowest.

Patient
Age
Donor Criteria O A B AB
U.S. Average Pediatric SCD 0y 11m 0y 10m 1y  0m 0y  7m
U.S. Average Adult SCD 3y 12m 2y  7m 3y  8m 1y 11m
U.S. Average Adult ECD 2y 10m 1y 11m 2y 12m 1y  5m

The table below shows the typical wait time for adult patients receiving a kidney transplant from a standard criteria donor at three large transplant centers in different parts of the country. Note that although Univ. Wisconsin in Madison is geographically close to Northwestern Memorial Hospital in Chicago, it is in a different  donor service area that excludes the large cities of Chicago and Milwaukee, resulting in significantly shorter wait times.

Patient
Age
Donor Criteria O A B AB
UCLA Med. Ctr. Adult SCD 8y  6m 7y  5m 7y  1m NA
Univ. Wisc. Med. Ctr. Adult SCD 2y  7m 0y  4m 1y  4m 0y  1m
Northwestern Mem. Hosp. Adult SCD 3y  6m 3y  4m NA NA

The table below shows the typical wait times for the five transplant centers within Washington state. All are within the donation service area for LifeCenter Northwest. Excluding Seattle Children’s Hospital, wait times do not vary greatly between hospitals, except Swedish Medical seems to have a longer wait times than the others. (I can’t explain it, nor can I determine if it is statistically significant.)

Center Name Patient
Age
Donor Criteria O A B AB
Seattle Children’s Hospital Pediatric SCD N/A N/A N/A N/A
Sacred Heart Med. Ctr. Adult SCD 3y  7m 2y  4m N/A N/A
Swedish Med. Ctr. Adult SCD 3y 10m 2y  8m 2y  8m N/A
Univ. Wash. Med. Ctr. Adult SCD 3y  1m 2y  1m 2y  8m N/A
Virginia Mason Med. Ctr. Adult ECD 3y  0m 1y  9m N/A N/A

Typical wait time underestimates average wait time

Calculating a median wait time for patients receiving a transplant during a year is not the same as the median wait time for all patients. That’s because patients who did not receive a transplant during the year are not included in the calculation.

Also note that for open-ended data like wait time, the median will be much lower than the mean. Some hard-to-match patients (specifically, those  with high sensitivity to HLAs) wait much longer than others. They may also be more likely to exit the list prior to transplant, meaning they are not included in the wait time calculation.

The median wait time of patients who receive a transplant understates the expected wait time even more in states like California where the wait time is very long and more than half of patients entering the waiting list never get a transplant. That is, the total patient median wait time is undefined. Patients exit the waiting list for a variety of reasons including death, becoming too ill for transplant surgery, or losing contact with their transplant center.

So why not include all patients in calculating a median wait time? That’s because some patients on the UNOS waiting list are not actually ready to receive a transplant. Some patients are on the so-called inactive list, meaning they are not considered a suitable candidate for a transplant. Including all patients when calculating a median wait time would skew the median wait time too high. But it isn’t desirable to exclude all inactive patients from the calculation either. That’s because patients move back and forth between the active and inactive list. Some patients who receive a transplant are still listed as inactive at the time of surgery. For a detailed discussion of the active and inactive waiting lists, see this Apr 2010 blog post.

A note about cPRA score

The most common measure of the level of sensitivity to HLAs is called the calculated panel reactive antibody (cPRA). It is the percentage of donor organs that would be expected to be incompatible to the patient. The level can vary from 0% to 99%. Most patients have low cPRA level and that is captured in a median wait time. However, high cPRA patients wait much longer. The median wait time for all patients is not a good estimate of their wait times.

One way of improving the accuracy of the wait time calculator would be to include cPRA level as one of the independent variables. However, many patients do not know their cPRA score and Arbor Research did not want to discourage patients from obtaining potentially useful information on wait times.

Also, the median wait times are calculated on individual cells and adding cPRA would make each cell too small to calculate a median. Arbor Research plans to update the wait time calculator soon. It expects to use a random-effects model rather than a simple median for each cell. This should allow estimating a wait time for cells that currently have no estimate and to include additional variables like cPRA so as to produce better wait time estimates for highly sensitized patients.

by George Taniwaki

Cold perfusion device

The Associated Press just reported the first successful use of a warm perfusion device during a transplant performed in the U.S. The headline of the article says “Beating heart transplants tested.” The operation was an important milestone, but the headline overstates the case a bit.

First, some background. Historically, organs recovered from deceased donors are placed in a preservative solution, packed in sterile ice, and placed in a standard picnic ice chest for transport to the hospital that will perform the transplant into a patient needing the organ.

Kidneys, because they are the most commonly transplanted organ, get slightly better treatment. Each kidney is placed in specially designed transport device that perfuses (pumps) a chilled preservative around the kidney. The most common one is called LifePort, produced by Organ Recovery Systems of Chicago. It looks like a very large egg, with a white body and lid, and a light blue stripe in the middle that contains a display console.

I recently took a tour of the facilities of LifeCenter Northwest, the organ procurement organization for the northwestern region of the U.S. They have several LifePort devices in their surgical storage room, all lined up and ready to go at a moment’s notice.

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LifePort perfused kidney transport container. Image from IDEO

The use of a cold perfusion device can extend the useful life of a donated organ by more than 24 hours, nearly doubling the useful storage and transport time of donated kidneys. Conversely, it can improve the quality of an organ for a given time in storage. Thus, use of cold perfusion devices can both increase the number of usable organs and improve patient outcomes.

Warm perfusion

The next improvement beyond cold perfusion, is warm perfusion. Keeping an organ warm reduces the damage caused by temperature change. But it requires a special perfusion solution that contains blood so that it can circulate oxygen to the cells in the organ. The organ also has to be carefully monitored to keep it within acceptable metabolic ranges. A company called TransMedics that was mentioned in a May 2010 blog post has developed such a device for heart transplants. It pumps an oxygenated solution through the heart in pulses, but does not keep the heart itself pumping. It is now in clinical trials as described in the AP article.

by George Taniwaki

A group from Swedish Medical Center (a transplant center in Seattle) and LifeCenter Northwest (the organ procurement organization serving Alaska, Northern Idaho, Montana, and Washington) climbed to the summit of Mt. Rainier yesterday and held a live webcast and chat.

It was all done as part of an effort to educate the public on the importance of becoming an organ donor.

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Video still from Swedish Medical Center

I missed the webcast, but I definitely support the effort. If you haven’t registered to be an organ donor, do it today. It only takes a few minutes. Just go to Donate Life website and register with the state where you live. Remember to tell your family about your decision. If you have an iPhone, you can download the DonateLives app.

Earlier this week, the California senate unanimously passed state SB 1395, which is now before the state assembly. This bill will make California a leader in trying to ease the shortage of organs for transplantation. This is significant because currently California has the longest transplant waiting lists (for both average wait time and total number of patients) in the country.

Last year, Steve Jobs, the founder and CEO of Apple and who lives in California, received a liver transplant in Tennessee. He was on the waiting list in both states. He put himself on multiple lists because it increased his chance of getting an organ quickly. The waiting time for a transplant varies considerably. In California the median wait time for a liver is over three years while in Tennessee it is only about four months. (Mr. Jobs’ case was mentioned in an Apr 2010 blog post.)

After this experience, Mr. Jobs lobbied Gov. Arnold Schwarzenegger to push for changes in California law to improve access to organs. The two of them appeared at a press conference in March to announce the introduction of state SB 1395. A really good description of Mr. Jobs’ role is given in Business Insider Apr 2010.

JobsSpeaksl When Jobs speaks, Schwarzenegger listens. Photo from Business Insider

The bill does a couple of things. First, it makes a seemingly minor change to the procedure required to get a drivers’ license. Currently, applicants are told that they can indicate on their licenses that they want to be organ donors upon death. Those that agree have a pink dot added to their license, a process called opt-in. The bill would change this to require that all applicants declare whether they want to be organ donors or not, called mandated choice. Previous research indicates that about only about half of people who would donate actually bother to sign up (New York Times Sep 2009). Thus, mandated choice may double the number of declared donors.

Incidentally, not all states actually compile and distribute a registry of organ donors based on DMV records. In states without a registry it is up to each hospital to get donor information from the patient. Further, in the U.S., regardless of what is stated on the patient’s driver license, organ procurement organizations (OPOs) always seek permission from family members prior to harvesting organs and tissue from a deceased patient. In one-fifth of cases, family members do not honor the wishes of the deceased and refuse to allow the organs to be removed. So if you want to be a donor, it is important to make your wishes known to your family members.

Also note that mandated choice is different from presumed consent, in which people are presumed to be willing to donate unless they state that they want to opt-out. Presumed consent is controversial and unlikely to be adopted anywhere in the U.S., though it is under discussion in Illinois, New York, and possibly other states. Several countries, including Spain and Greece, use it. These countries have higher deceased donation rates. However, it turns out there is an inverse correlation between deceased donor rates and live donor rates. Transplants from live donors provide much better medical outcomes than transplants from deceased donors. Thus, presumed consent may actually be detrimental to the goal of improving patient outcomes.

The second impact of the California bill will be to establish an Altruistic Living Donor Registry, a list of people willing to donate a kidney to a stranger. They would be matched with compatible recipients on the UNOS waiting list. Since there are over 10,000 Californians on the waiting list, any person who signed up to be a donor would be matched almost immediately. So it is unlikely there would actually be a donor list.

***

A story about California’s proposed Altruistic Living Donor Registry in the San Fran. Chron. Apr 2010 focuses on the experience of David Jacobs a kidney transplant recipient who later founded Silverstone Solutions. Silverstone’s Matchmaker software was mentioned in a Mar 2010 blog post.

[Update1: I erroneously stated in the fifth paragraph that no state maintains a registry of donors. Most states do. Much thanks to Alvin Roth at Harvard for pointing out that the Massachusetts DMV maintains the registry that it then shares with the OPOs. In addition to having a sharp eye, Mr. Roth is an expert on market design and a founder of the New England Program for Kidney Exchange. His work is mentioned in a Mar 2010 blog post.]

[Update2: Gov. Schwarzenegger signed SB 1395 in Sep 2010.]

As I continue to gather materials for my kidney recipient community outreach effort, I want to learn more about the educational activities of the Northwest Kidney Centers. Today (May 12), I attended the NKC Breakfast of Hope, an annual fundraiser. It was held at the Westin Seattle. More than 800 people participated, raising over $375,000.

Jesse Jones, an Emmy Award winning reporter for King 5 television in Seattle, was the master of ceremonies. He related a story, which I was unaware of, that one day he noticed blood in his urine. He went to the doctor and the next morning his wife answered the phone. It was the doctor who said the tests indicated he had kidney cancer and wondering if he could come in that afternoon to prepare for surgery.

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Jesse Jones, master of ceremonies. Photo by Mike Nakamura

Joyce Jackson, the CEO of NKC made some remarks. One particular sentence really stuck in my mind, “There are 273 patients at Northwest Kidney Centers waiting for a kidney transplant. Our goal is to get that to zero.” By stating the problem in this way she makes the goal seem achievable. Almost everyone else who talks about reducing the wait list starts with the 85,000+ people on the national list. That big number makes it seem like an insurmountable goal, and that no single person could ever make an impact. (See a Jun 2010 blog post for more on how framing numbers affects us.)

The keynote speaker was John Piano, CEO of Transplant Connect. This LA-based company provides the software used by organ procurement organizations (OPOs) to facilitate the matching of donor organs with transplant recipients. The company was mentioned at the end of a Mar 2010 blog post.

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John Piano, keynote speaker. Photo by Mike Nakamura

At the breakfast, I was seated next to Cathy Pelzel, an executive assistant at SightLife. This organization, formerly known as Northwest Lions Eye Bank, recovers and places eye tissue for transplants. It turns out she is also a kidney donor, giving a kidney to her niece over 25 years ago. The graft is still functional, showing the real advantage of live donor kidneys.

Cathy pulled out her smartphone and launched the calendar app, highlighting the anniversary date of her donation. I hadn’t really thought about how I will feel about my donation date. Will I mark the occasion every year? Will my recipient? I wonder how other donors and recipients feel about their anniversary date.

****

The breakfast meal itself featured a kidney-friendly menu. Surprisingly, it included items like sausage, crepes, and chocolates. But it excluded orange juice, sugary pastries, and highly salted eggs. Preparing a kidney-friendly diet means being careful, but doesn’t mean bland. (More on that in a June 2010 blog post.)

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A Breakfast of Hope guest discovers that a kidney-friendly menu need not be bland. Photo by Mike Nakamura

The NKC premiered a heartwarming video featuring the story of Dave LeFevre and Bill Hewlett. Dave is a Microsoft employee who donated a kidney to Bill, a fellow church member.

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Breakfast of Hope 2010. Video still from NKC

After the breakfast, I introduced myself to Dave and Bill. Dave said that if he was a speaker, he would have said that the people in the room could solve the waiting list just by signing up to be a live donor that day. (Well, except for the many people in the room who only have one kidney because they’ve already donated the other one.)

by George Taniwaki

Current donor kidney preservation technology

Kidney transplant surgery has a rather unusual characteristic. It is normally performed on an emergency basis, but it is not a critical life-saving procedure. Let me explain.

Once a person is diagnosed with end-stage renal disease (ESRD), they will require immediate renal replacement therapy or else they will die. However, that doesn’t mean they need an immediate transplant. That’s because dialysis technology is now quite reliable and dialysis equipment is widely available in all major cities. In fact, a patient can live several years on dialysis. Thus, kidney transplant surgery is usually performed as an elective procedure rather than a critical procedure.

Most kidneys come from deceased donors and the quality of the organ is dependent on the length of time it lacks blood circulation. There are two stages for measuring this time. The first is the time the kidney is cut off from circulation while still inside the body of the deceased donor (known as warm ischemia time). The seconds is the time the kidney is kept cool in a preservative solution (known as cold ischemia time).

Current preservation solutions are not very effective and the number of cells in the organ that die while the organ is not getting blood flow can be quite high. If the ischemia time is too long, the organ function is reduced which worsens patient outcomes (Arch. Surgery Sep 2000). And as the transport time increases, the more likely it is that the receiving surgeon will reject the organ and it must be discarded (Amer. J. Transpl. May 2007). Thus, there is often a large rush and expense to fly organs to the receiving hospitals. Meanwhile the receiving hospitals need to contact the recipients and quickly get them to the hospitals and prepared for surgery. (Note that this urgency only applies to deceased donor surgery. Live donor surgery like mine can be scheduled days or weeks in advance.)

A better solution may be the solution

An article in today’s Tech. Rev. points to an interesting collaboration between Hemant Thatte, a cardiothoracic researcher at Harvard’s medical school, with three students from Harvard’s business school. The students became aware of Mr. Thatte’s experimental preservative solution called Somah (Circulation Nov 2009) that can extend the time organs can be preserved prior to transplantation, or conversely, improve the quality of the organs for a given ischemia time. In a study using pig hearts, after 4 hours of storage at 4°C, hearts preserved with Somah had much better cell structure and function than those preserved using the standard solution.

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Heart perfusion test. Photo from Harvard

The students decided to write a business plan for this preservative solution. They formed a company called Hibergenica and are seeking $5 million in venture capital financing to complete medical studies and file for FDA approval. Their collaboration was featured at the Univ. Res. Entrepreneurship Symp. 2010 held recently in Cambridge.

The business plan projects the market for preservative solution to grow from $30 million today to $200 million if Somah can be sold for five times the price of the current solution and some market growth occurs because more organs that would normally be discarded are instead preserved and shipped to a distant transplant center.

Warm perfusion

The Tech. Rev. article points out that there is another competitor worth watching. TransMedics in nearby Andover has developed the first portable warm blood perfusion system. By pumping oxygenated blood and a preservative solution through the harvested organ, it avoids the damage caused by ischemia. In fact, the company claims that by using their device, an organ can be resuscitated and its function improved while waiting for transplantation.

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 Warm perfusion test. Photo from TransMedics

[Update: Clinical trials have started for the TransMedics device, see this Nov 2010 blog post.]