In an Aug 2010 blog post, I discussed the prospects for regenerative medicine to alleviate the shortage of transplantable organs. Regenerative medicine usually starts with an organ obtained from deceased donors. But the organ itself isn’t used. Instead the cells are removed and the remaining scaffold is seeded with stem cells to create a new organ. Near the end of that blog post I mentioned that there was work being performed by David Hume and others at the Univ. of Michigan to produce an external device that could perform some of the endocrine functions of a kidney. It would supplement an external dialyzer to provide complete kidney function for a patient with end-stage renal disease.

Recently, Univ. California, San Francisco issued a press release stating that Shuvo Roy and other researchers in the Department of Bioengineering and Therapeutic Sciences have reduced the size of both devices by using a combination of micro-electromechanical systems (MEMS) and human kidney cells. Their prototype is about the size of a coffee cup, or similar in size to a kidney. They hope the device will be implantable, leading to a portable, artificial kidney. Much work remains and they don’t expect clinical trials to begin for another five to seven years. Yet, the promise is great. Such a device could help improve the medical outcomes and quality of life of all patients with ESRD, meaning both those waiting for a transplant and those who would otherwise receive dialysis therapy.

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Artificial kidney. Video from UCSF

[Update: Replaced the cutaway view with a video.]

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.

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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.)

The kidney transplant waiting list maintained by the UNOS gets longer every year as does the average waiting time for patients on the list. This is true even though the number of patients diagnosed with end-stage renal disease (ESRD) has declined slightly over the past few years. What is driving this? To examine this problem, I examined the data for annual changes in the number of patients with ESRD and the number on the waiting list.

About the data

The data for annual incidence (number of new cases of ESRD diagnosed in a year) and prevalence (total number of people with ESRD at the end of each year) were obtained from the USRDS 2009 annual report. The report contains a wealth of data on chronic kidney disease and ESRD. It has an entire chapter devoted to transplantation.

The data on the UNOS waiting list data was obtained from the UNOS. Some is available from OPTN annual reports or from the report builder web service. Others were generated specifically for me by UNOS. I want to thank Katarina Linden of UNOS for summarizing the SAS data used in this blog post. Any errors in analysis are mine alone.

A few notes regarding the UNOS data. First, the data being analyzed is for the kidney-only list. Patients are placed on lists based on what organ(s) they need. The UNOS maintains separate lists for each organ combination a patient needs, kidney only, kidney and pancreas, kidney and liver, etc. A single patient can be on more than one list. If the candidate receives a transplant, the transplant center is required to remove the patient from all the other lists as a duplicate entry.

Second, the counts are for registrations not candidates. In any year, about 5% of the kidney-only candidates (patients on the kidney-only waiting list) are registered at more than one transplant center. Most are people who have moved and are transferring their registration to a transplant center closer to their new address. But a few, most likely wealthy patients, are actually registered at multiple transplant centers in an effort to get an organ faster. The most famous example of this is Steve Jobs, who needed a liver transplant and had access to a corporate jet. But anybody who lives in a large city can benefit by getting on the list at a hospital in a more rural area, then traveling to that town and waiting for a donor after they reach the top of the list. Again, after the patient receives a transplant, all transplant centers are required to inform the UNOS that duplicate registrations for that patient should be removed from the list.

Third, there isn’t a direct correlation between the number of people on the UNOS waiting list and the number of people with ESRD (the prevalence rate). Once a patient receives a transplant, they are removed from the waiting list. However, they are not cured and so are still counted as having ESRD. Similarly, there is no direct correlation between the number of people added to the UNOS waiting list in a year and the number of people newly diagnosed with ESRD. That’s because a patient who enters the waiting list may have been diagnosed with ESRD years earlier. Also, they may enter the waiting list if the they previously received a kidney transplant and the organ fails.

Finally, there are two categories to the waiting list. Registrants are classified by the transplant center as either active and inactive. Active registrants are considered medically able to get a transplant immediately if an organ becomes available. Inactive registrants are currently unable to accept a transplant, but are considered good long-term candidates for a transplant. I will discuss this in more detail later.

The UNOS data is collected via a survey that each transplant center must complete for each registrant on their waiting list once a year to determine the registrant’s current status. As any of you who have dealt with survey data realize, cleaning survey response data from respondents (both the candidates and the administrators at the transplant center) who are not familiar with statistical analysis is one of the most difficult tasks in any research project and is a major source of nonsampling error.

Growth in prevalence of ESRD and in size of kidney transplant waiting list

In 2007, the latest year data is available, about 111,000 people in the U.S. were diagnosed with ESRD for an average incidence rate of 361 per million population. Figure 1 shows the incidence rate of ESRD has been rising dramatically over the past two decades, though it seems to have peaked. Blacks are more than three times likely to be diagnosed as whites. The ratio of prevalence by race is not as high, meaning that once diagnosed, whites tend to live longer with ESRD than blacks.

Incidence

Figure 1. Incidence and prevalence rates for ESRD by race. Data from USRDS

In 2007, the prevalence of ESRD was about 1,700 per million population, representing over 527,000 people. Of these people, about 150,000 have a functioning transplanted kidney and 375,000 are on dialysis. (The remainder refuse treatment and will die within a few months.) However, as shown in Figure 2, there were only 78,300 registrants (and fewer candidates) on the UNOS transplant waiting list. This means only one-fifth of patients on dialysis were on the UNOS waiting list. As discussed in earlier blog posts (Dec 5 and Dec 18), the reasons people fail to get on the waiting list are complex.

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Figure 2.Total active and inactive wait list. Data from UNOS

Figure 3 shows even though the number of transplants is growing (right), the incidence rate of ESRD is growing faster (left), so the wait times for a deceased donor kidney is getting longer (center) and the transplant rate is falling (left). For every 100 people newly diagnosed with ESRD in 2007, there were only four transplants.

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Figure 3. Transplant trends. Data from USRDS

Growth in the UNOS waiting list

Figure 4 shows the number of new registrants being added to the active list each year rose from about 17,000 in 1995 to 25,000 in 2004 and has flattened out since then. Unfortunately, the number of transplants, from either deceased or live donors, has not kept pace. The seemingly good news is that the number of registrants removed from the active list without a transplant (which consists of people who decide they no longer want a transplant, are too sick for a transplant, or die) has not been growing. The categories that has been growing (and growing rapidly) are movements to and from the inactive list, with more patients going to the inactive list than coming from it. Notice the size of this churn represents a large proportion (more than one-fourth) of the active waiting list population.

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Figure 4. Active wait list. Data from UNOS

Figure 5 shows the rapid growth of the inactive waiting list. First, notice the jump in the number of new inactive registrations starting in 2004. The most common reason for being initially placed on the inactive list is an incomplete evaluation by the transplant center. That is, the patient starts the evaluation process but is unable to complete it before the survey date (perhaps due to difficulty getting transportation to the transplant center). Other reasons for being on the inactive list are the presence of treatable comorbidities such as obesity, addiction (smoking, alcohol, or drugs), hypertension, or type 2 diabetes.

Next, notice the large number of registrants moving to the active list. Many of them are the new registrants who have completed their evaluations and are moved to the active waiting list, but also includes a large number of registrants who started as active and were on the inactive list for a period of time.

Most of the people on the inactive list are removed without a transplant, which makes sense, since they were not considered good transplant candidates. However, when coupled with the large flow of registrants from the active list (equal to about half of the total number of inactive registrants each year), this may also indicate that many transplant centers are moving active candidates to the inactive list rather than removing them entirely. Thus, the inactive list may contain many registrants who are too sick to receive a transplant and have little chance of recovery prior to death.

There are a large number of registrants in the Not coded category. This indicates that people on the inactive list are less likely to be in close contact with their transplant center and either could not be contacted or incorrectly completed the survey.

Inactive

Figure 5. Inactive wait list, data from UNOS

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In a future post, I will continue to explore the USRDS and UNOS data to revisit the issue of long wait times experienced by patients with type O blood.

[Update1: Added explanation that the counts of incidence and prevalence cannot be directly compared to the counts on the waiting list.]

[Update2: Corrected an error in proportion of patients with ESRD on the UNOS waiting list. Patients who have a functioning transplant should be excluded from the calculation.]

by George Taniwaki

Today is a double kidney day for me. First, it is a kidney day for everyone; it is World Kidney Day. This day is a part of a global health awareness campaign organized by the International Federation of Kidney Foundations and the International Society of Nephrologists. The society is celebrating its 50th anniversary in 2010. The theme of this year’s World Kidney Day is “Protect your kidneys: control diabetes.”

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Kidney disease is often treatable if the condition is detected early. This means more people with diabetes, hypertension, or a family history of kidney disease need to be educated about the disease and get tested. A poignant yet understated video emphasizing the importance of testing is available on YouTube.

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Second, it is a personal kidney day for me. I just received a letter from the University of Washington Medical Center. The transplant committee has accepted me as a living donor. That means all four interviewers (social worker; nephrologist; surgeon Oct 12 and Mar 5; and psychiatrist) approve of my participation and that all medical test results (x-ray, ECG, CCR, PPD, and blood panel; CT scan; and split renogram) were within the acceptable ranges.

Now it’s just a matter of finding a recipient match and scheduling the surgery date. My first choice is to be matched with a patient on the National Kidney Registry to start a chain. But that may be unlikely since I have AB+ blood type (see Sept 2008). I’ve been on the NKR waiting list for over two years now without a match. So if I don’t find a match from the NKR list, then I will donate to the next compatible patient at UWMC based on the UNOS waiting list.

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My acceptance letter arrives on World Kidney Day. Image from UWMC

For more information on becoming a kidney donor, see my Kidney donor guide.

[Update: Clarified that the patient I will donate to at UWMC is on the UNOS waiting list. The UWMC and UNOS do not maintain separate waiting lists.]

In my last blog post, I hinted at a possible conflict of interest between transplant centers and the dialysis industry. That is, transplant centers want to encourage all of their patients with end stage renal disease (ESRD) for whom renal replacement therapy is medically advisable to consider the option. On the other hand, dialysis centers, equipment manufacturers, and pharmaceutical companies believe that they are providing the best treatment option for their patients.

Another Dec 2009 blog post hints at this conflict of interest by noting the low-level of compliance by dialysis treatment centers to the Medicare requirement that they inform patients of the renal replacement therapy option and help patients get on the UNOS waiting list. Dialysis centers want their patients (customers) to be comfortable. It is unlikely the staff wants to make patients anxious by consistently reminding them of the need to find a donor, get a transplant, and get off of dialysis. Further, patients have much more contact with the personnel at the dialysis center, where they go several times a week for several hours per visit, than they do with the physicians at their local hospital (which may not be a transplant center) or with transplant nephrologists or surgeons at a transplant center. Thus, to avoid cognitive dissonance, patients may discount advice they receive from physicians to find a donor since it is an emotionally difficult task and conflicts with the patient’s image of good care they are getting from the dialysis center.

In an earlier blog post, I noted that current Medicare policy misallocates resources by subsidizing expensive dialysis for the life of the patient but limits subsidies for immunosuppressant medication to only three years after a kidney transplant. I support the addition of lifetime coverage for antirejection drugs proposed in the House and Senate versions of the health care reform bill. I thought this was uncontroversial. However, the issue is more complex than I first believed.

A story in the Dec 14, 2009 New York Times points out that adding this coverage may have the unintended consequence of causing dialysis centers in rural areas to close. This is because the bill will reduce Medicare reimbursement rates for dialysis treatment. Dialysis centers with a higher proportion of Medicare patients will be hurt the most, as will smaller dialysis centers, which tend to have higher fixed costs, The centers most likely to be affected are in rural areas which serve sparsely populated regions and serve an older population that is less likely to have private insurance. Many of them may be forced to close. The Kidney Care Partners, a coalition that includes kidney patients, dialysis centers, pharmaceutical firms, equipment manufacturers, and the National Kidney Foundation, is lobbying Congress to not allow this to happen, even if this means dropping the increased coverage for antirejection drugs.

This is stupid. There is no reason to link these two actions. Increasing funding for post-operative medications will encourage more kidney patients to seek a transplant and make it more likely that patients that do get a transplant will adhere to their drug regimen. This will enhance patient quality of life, potentially increase longevity, and possibly even reduce overall Medicare costs. Reducing Medicare reimbursement rates for dialysis will reduce costs, but it does nothing to encourage patients to switch their treatment from dialysis to renal replacement.

[Update 1: I added a final paragraph explaining that the two funding decisions should be independent.]

[Update2: The Senate version of the health care bill, H.R.3590, passed on Dec 24. It does not contain the provision to extend Medicare coverage for immunosuppressive drugs or to reduce payments to dialysis centers.]

A recent (Dec 2009) blog post discussed the issue of kidney patients with end stage renal disease (ESRD) who get on the UNOS transplant waiting list, but are unable to get a donor organ. Today’s entry will explore the problem of kidney patients who for some reason don’t ever get on the waiting list.

Not all patients with ESRD are good candidates for transplants. For instance, they may have one or more comorbidity factors (specifically, they are not healthy enough to undergo surgery, had cancer within the past five years, have heart disease, or have type 2 diabetes). These patients won’t get on the waiting list. However, some patients don’t get on the list for the wrong reasons. For instance, because of miscommunication, some patients are never informed that renal replacement therapy is an option for them. Among patients who are told, some decide they don’t want the transplant surgery.

All patients with ESRD should be told that a transplant is the preferred option when it is medically advisable. However, it is not clear how many patients are told this or understand it.  In a report published in Dec 2009 Pittsburgh Tribune-Review, investigators looked at Medicare records and found that at many dialysis clinics none of the patients have been informed of the transplant option and the centers had no patients on the transplant waiting list. However, the story concedes this may be due to a timing issue. The Medicare forms are filled out when the patient first visits the clinic and the patient may not be informed at that time. The records are not updated if the patient’s status changes at a later date.

Some patients don’t get on the list because of biases (possibly unconscious) by doctors when advising patients. For instance, a study published in the Oct 1999 Health Services Research shows that patients with only Medicare insurance coverage (who are more likely to be minority, female, and poor) were less likely to be placed on the U.S. transplant waiting list than patients with private insurance. Since the research only looked at statistical data rather than conducted patient interviews, it isn’t clear if the result is because 1) patients without insurance are actually less likely to be good candidates, 2) doctors are less likely to inform patients without insurance of treatment options, or 3) the patients were advised, but did not follow through. In any case though, nephrologists should be made aware of the potential bias and take steps to ensure their advice and actions do not discriminate against patients based on insurance status, race, gender, or income.

Another study in Jan 2009 J. Amer. Soc. Nephr. (subscription required) found that women over 45 are less likely to be placed on the kidney transplant list than men. This bias persists even though women are as likely to survive as men.

A study in Oct 2009 Amer. J. Transpl. (subscription required) found that African-Americans were 27% less likely than Caucasians to be recommended for kidney-pancreas transplants. Hispanics were 25% less likely to be recommended. The authors speculate that some of the bias may be due to physicians incorrectly assuming that African-Americans have type 2 diabetes and are thus ineligible for a two-organ transplant. Changes in Medicare legislation in 1999 to cover two-organ transplants increased transplant rates for all races, but did not close the gap.

Even if a patient gets on the waiting list, they may not get an organ. A study in Feb 2008 J. Amer. Soc.  Nephr. (subscription required) found that the more obese a patient was (as measured by body mass index or BMI), the more likely the patient was to be skipped for another patient on the list. It is possible that these patients had other comorbidity factors that disqualified them for a transplant, but it may also be due to a bias toward selecting non-obese patients.

What about patients who are informed of the transplant option but decide they don’t want to be placed on the list? One possible reason is that they believe that a kidney transplant should be a last resort, after undergoing dialysis. Until I decided to become a kidney donor, I thought the preferred treatment for kidney patients with ESRD was to first try dialysis and if that failed, then get a transplant. However, that is not true. Studies have shown that if the patient is a suitable transplant candidate, then an early transplant, called a preemptive transplant, results in superior outcomes and is the preferred treatment. Dialysis is used only because of the shortage of organs. Unfortunately, a recent survey reported in Nov 2009 Amer. J.  Nursing shows that up to half of kidney patients believe that dialysis must precede a transplant and 60% viewed transplantation as a last resort.

Another potential reason that a kidney patient with ESRD would decline a transplant is fear of surgery. A focus group of medical professionals conducted in South Carolina revealed fear of surgery to be one of six perceived barriers to living donor kidney transplantation among African-Americans. The results are reported in June 2006 J. Natl. Medical Assoc. The emotional stress continues after receiving an organ transplant and fear of this may also discourage accepting a transplant.

Finally, concerns about the cost of surgery and the ongoing costs of immunosuppressive medication may discourage some patients. As mentioned in an Sep 2009 blog post, Medicare covers the cost of dialysis but not antirejection drugs. So even though dialysis is expensive and leads to lower quality of life, some patients may choose it rather than a transplant because it is more affordable for them.

[Update: I added a paragraph about an article in the Pittsburgh Tribune Review.]