UNOS DonateLife

June 1, 2012

UNOS Researchers Present Studies at American Transplant Congress

Boston – Researchers from United Network for Organ Sharing (UNOS) authored and will present several studies at the American Transplant Congress (ATC), a joint meeting of the American Society of Transplant Surgeons and the American Society of Transplantation held June 2-6 at the John B. Hynes Convention Center. UNOS staff members are primary authors of a total of eight papers.

NOTE: Some of these studies were supported wholly or in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Below is a listing of studies in which UNOS researchers are primary authors. UNOS staff researchers are indicated with an asterisk.

The Organ Procurement and Transplantation Network Kidney Paired Donation Pilot Program: Review of Current Results

Embargo until Sunday, June 3 – 4:00 p.m. EDT
Authors: Ruthanne L. Hanto, RN, M.P.H., CPTC*, Kenneth A. Andreoni, M.D., John J. Friedewald, M.D., Elizabeth F. Sleeman, M.H.A.*, Catherine B. Monstello, CPHQ, RRT*, Darren E. Stewart, M.S.*

The authors reviewed early experience from the kidney paired donation pilot program initiated by the Organ Procurement and Transplantation Network (OPTN) in October 2010. As of the abstract submission date, 13 transplants had been performed with another four pending. The vast majority of candidates submitted by participating transplant programs presented challenges in matching, because they had an O blood type and/or had a high level of immune sensitization (a calculated panel reactive antibody level, or CPRA, of 80 percent or higher). Even so, of the 17 transplants performed or scheduled during the study period, four recipients were blood type O and five were highly sensitized. The researchers observed that for greater success with the program, more transplant centers need to participate and centers should list more donor/candidate combinations who are easier to match (for example, potential non-directed donors who are blood type O).

In addition, a number of potential matches have been declined due to unacceptable antigen combinations as determined by the center listing the candidate. The authors noted that the match decline rate could be decreased if centers list unacceptable antigens more accurately, but that listing more unacceptable antigens could also limit potentially acceptable offers for highly sensitized candidates.

Living Kidney Donor Deaths within 2 Years of Donation

Embargo until Monday, June 4 – 4:00 p.m. EDT
Authors: Jennifer L. Wainright, Ph.D.*, David M. Kappus, M.A.S.*, Maureen A. McBride, Ph.D.*, Sarah E. Taranto*, Christie P. Thomas, M.B., FRCP, FASN, FAHA

As with any form of surgery, living kidney donation involves a small risk of death. For the benefit of living donors and clinicians to assess potential risk, it is important to study deaths within a short time after donation to assess how many may be associated with the procedure.

The researchers examined living kidney donors who donated between October 1999 and March 2011. They found and analyzed 93 instances where donors died within two years of donation, identified either through centers’ reports to the OPTN or through searching the Social Security Death Master File. Among the 93 deaths, 25 occurred within 90 days of donation.

Many deaths occurred from causes apparently unrelated to donation, including accidents, homicides, or deaths in the line of duty. However, 27 of the 93 deaths within two years (approximately 0.04 percent of more than 70,800 living donors in the study period), and 17 of the deaths within 90 days of donation, were medical in nature and did not fall into other categories. A specific cause could not be identified in 23 other deaths within the two-year period (one within 90 days), while nine deaths resulted from cancer and another nine were the result of suicide.

The authors concluded that the occurrence of death within 90 days of donation from causes most likely to be donation-related (either medical in nature or unknown) is small (0.025 percent among more than 70,800 donors), with no evidence of changing rates of death by year over the last decade. However, they add, the occurrence of suicide and cancer deaths within the two-year period emphasizes the importance of thorough pre-donation psychosocial and cancer screening.

Has Broader Sharing for Pediatric Status 1A and 1B Heart Candidates Reduced Waiting List Mortality?

Embargo until Monday, June 4 – 4:00 p.m. EDT
Authors: Wida S. Cherikh, Ph.D.*, Leah B. Edwards, Ph.D.*, Marissa A. Clark, M.S.*, David M. Campbell, M.D.

A major change was implemented to pediatric heart allocation policy in May 2009. The revised policy was intended to increase geographic access to pediatric donor hearts for the two most urgent categories of pediatric heart candidates (Status 1A and 1B). Previous studies have indicated significant decreases in waiting list deaths and increases in transplant rate for adult Status 1A and 1B candidates after broader sharing of hearts was first implemented in 2006.

This policy had the potential to affect pediatric transplantation greatly since more than 80 percent of heart candidates first listed before one year old, and more than 60 percent of those first listed between ages 1 and 17, have been Status 1A at some point. The researchers studied the effect of the policy on Status 1A and 1B pediatric candidates by comparing respective 17-month periods before and after the policy’s implementation date.

After policy implementation, waiting list death rates decreased for Status 1A and 1B candidates in all pediatric age groups. Also following policy implementation, both the number and percent increased among pediatric Status 1A candidates receiving hearts from pediatric donors within a 500-mile radius, while the percentage of transplants for pediatric 1B candidates increased involving pediatric donors located 500 to 1000 miles from the recipient center.

Do Outcomes for Pediatric Status 1A Heart Candidates and Recipients Differ by Device Type?

Embargo until Monday, June 4 – 4:24 p.m. EDT
Authors: Wida S. Cherikh, Ph.D.*, Leah B. Edwards, Ph.D.*, Steven A. Webber, M.B., Ch.B., MRCP, Yulin Cheng*, David M. Campbell, M.D.

Since the majority of pediatric heart transplant candidates are listed as Status 1A, the allocation priority among this group will be determined largely by waiting time. The researchers compared the probabilities of waiting list death and receiving a transplant among pediatric Status 1A heart candidates based on whether they had some form of mechanical cardiac assistance or support and, if so, what device was used, over a four-year period of listings. They also analyzed post-transplant patient survival at one year for the candidates who were transplanted.

Among the groups studied, candidates who were on extracorporeal membrane oxygenation (ECMO) at listing had the highest probability of waitlist death, lowest probability of transplant and lowest one-year post-transplant survival. In contrast, candidates with a left ventricular assist device (LVAD) had transplant probabilities and a survival rate similar to Status 1A candidates who had no assist device. In considering a potential allocation system based solely on waiting list mortality, Status 1A candidates on ECMO might be considered to have a higher priority than the other Status 1A candidates. In considering a potential allocation system based on transplant-survival benefit, candidates with other device types might receive higher priority.

Smoothing It Out: Creating a Sliding Scale for Assigning CPRA-Based Allocation Points

Embargo until Tuesday, June 5 – 2:39 p.m. EDT
Authors: Darren E. Stewart, M.S.*, Anna Y. Kucheryavaya, M.S.*, Nancy L. Reinsmoen, Ph.D., John J. Friedewald, M.D.

Since October 2009, the OPTN has used calculated panel reactive antibody (CPRA) assessment to estimate the percentage of donors who would not be compatible with a given kidney transplant candidate based upon immune system rejection. Candidates likely to reject more than 20 percent of kidneys are considered “moderately sensitized”; those likely to reject 80 percent or more of kidneys are considered “highly sensitized.” Because highly sensitized candidates are biologically disadvantaged, they commonly wait much longer for a matching organ offer than those with lower levels of CPRA.

Current policy awards four kidney allocation points to candidates with a CPRA of 80 or higher to increase their likelihood of finding a compatible organ offer. However, no additional points are assigned to candidates with a CPRA at or near 100 percent, even though such highly sensitized candidates have a vanishingly small chance of finding a compatible donor. Similarly, all candidates with CPRA less than 80, including non-sensitized candidates, are treated the same and receive no points based on CPRA.

The researchers used data from deceased donor kidney offers in 2010 to evaluate the rate of offers per year on the waitlist candidates received by their CPRA level. The relationship between the offer rate and candidates’ CPRA was dramatic: As CPRA increased, the offer rate steadily decreased, with the exception of a spike when CPRA reached 80. As CPRA approached 100, though, the offer rate decreased to as few as 0.1 compatible offers per year for these very highly sensitized candidates, in spite of the awarding of four points.

The authors inverted the offer rate by CPRA curve to develop a “sliding scale” for assigning sensitization points along the CPRA continuum, starting with candidates having CPRA between 20 and 29, to candidates with CPRA of 100. Candidates with a CPRA between 80 and 84 would receive 2.46 extra allocation points instead of the current four. Candidates of increasingly higher CPRA (who are proportionally much harder to match as a result) would receive considerably more allocation points; for example, those with a level of 97 would receive 17.3 points.

The authors conclude that a sliding scale for CPRA points would be more effective than the current, somewhat arbitrary threshold of 80, and the entire curve could be adjusted to balance the priority of CPRA with other allocation factors. Offering allocation points beginning at a CPRA of 20, they suggest, may encourage centers to list more unacceptable antigens for even moderately sensitized candidates, thus potentially reducing instances where organ offers are ultimately rejected in final pre-transplant testing.

The authors also suggest that candidates with a score of 98 or higher may require national allocation priority in addition to extra points in order to compensate for their median wait of several years before receiving a compatible offer.

More Pediatric Status 1A Liver Transplants Are Performed after Broader Sharing of 0-10 Year Old Donors: Early Results

Embargo until Tuesday, June 5 – 3:03 p.m. EDT
Authors: Wida S. Cherikh, Ph.D.*, Marissa A. Clark, M.S.*, Heung Bae Kim, M.D., Simon P. Horslen, M.B.,Ch.B.

In November 2010, a change to liver allocation policy was implemented to broaden transplant access for medically urgent (Status 1A) pediatric liver transplant candidates and pediatric candidates needing a combined liver-intestine transplant. Status 1A pediatric candidates aged zero to 17 receive priority throughout their OPTN region, and pediatric candidates aged zero to 11 receive priority nationally, for organs from donors age ten or younger before local offers are made from these donors to any adult Status 1A candidates. To assess the policy’s effect, the authors studied respective nine-month periods before and after the implementation date.

In the post-implementation period, pediatric Status 1A liver candidates aged zero to 11 received transplants at a significantly higher rate, and the number of Status 1A transplants in recipients from donors aged zero to ten increased almost fourfold. While the number of pediatric combined liver-intestine transplants was too small to analyze in detail, there was no significant increase in death rates for liver-intestine candidates.

During the post-implementation time frame studied, no change was observed in waiting list death rates for adult Status 1A candidates or the percentage of transplants they received. While the policy appears to be meeting the goal of increasing pediatric transplants, the authors call for ongoing monitoring to ensure there is no negative impact on adult candidates.

Results of National Survey on Referral to Liver Transplant: The Transplant Program’s Perspectives

Embargo until Tuesday, June 5 – 5:30 p.m. EDT
Authors: Wida S. Cherikh, Ph.D.*, Silas P. Norman, M.D., Meelie A. Debroy, M.D., Deanna L. Parker, M.P.A.*, Henry B. Randall, M.D.

While liver transplantation is the most effective treatment for people with end-stage liver disease, little is known in summary about when and how often they are referred for transplant evaluation. The researchers surveyed to the surgical and medical directors of all U.S. liver transplant programs to study the timing and rate of referrals they receive.

Of the responding programs, all said they monitor patient referrals but only 61 percent monitor the number of eligible patients referred. While most respondents considered a MELD/PELD score of 15 as a cutoff for an early referral, some have no threshold. The most common reasons they said a referral may be delayed include a patient's noncompliance or substance abuse, financial/insurance constraints, medical comorbidities, and the patient’s unawareness that transplantation was a treatment option.

The researchers note that while many transplant centers report a lack of resources to determine whether all eligible patients are referred for transplantation, educational efforts are needed to encourage and improve timely referral.

What Will It Take? Kidney Programs Prove Resistant to Modifying Donor Acceptance Criteria in UNet^SM

Embargo until Tuesday, June 5 – 5:30 p.m. EDT
Authors: Darren E. Stewart, M.S.*, Kimberly H. Taylor, RN*, Jeffrey P. Orlowski, M.S., CPTC, Phillip A. Camp, M.D., Michael Angelis, M.D., Robert A. Metzger, M.D.

Maximizing the efficiency of organ placement – accepting an organ with the right characteristics for the right recipient – is a major goal of the transplant system. UNet, the computer program used for placement of deceased donor organ offers nationwide, allows transplant programs the opportunity to enter detailed criteria on offers they are willing to accept for one or more candidates.

The Effective Screening Work Group of the OPTN/UNOS Operations and Safety Committee has sponsored a number of educational efforts to help kidney transplant programs refine their donor acceptance criteria so that unnecessary organ offer refusals are minimized and kidneys can be placed most efficiently with programs willing to accept them. Yet a number of programs demonstrate a consistent pattern of refusals for organ offers with certain characteristics that could be programmed into their donor acceptance criteria.

The researchers provided data on kidney offer refusals to 43 kidney transplant programs and surveyed them. They also studied each program’s use of screening criteria, acceptance rate for imported kidneys, and volume of offers before and after the information was provided.

The majority of survey respondents indicated the data on their refusal patterns was helpful, but most cited significant obstacles to more detailed screening. Common stated reasons included the program’s philosophy of wanting to evaluate virtually all organ offers, time constraints in managing individual screening criteria for each candidate, and a concern that donor data may be updated or changed during the offer process and thus the center may consider accepting it based on new information. Only one of the 43 programs identified made substantive changes to its screening criteria during the time frame studied.

Many kidney transplant programs remain hesitant to rely on automated screening and carefully review each potential offer manually, which is their prerogative. Potential future refinements to screening criteria may reduce this reluctance for some programs. The authors recommend monitoring of acceptance patterns to ensure that programs are meeting their candidates’ needs and are not slowing the opportunity to place organs successfully.

The Organ Procurement and Transplantation Network (OPTN) is operated under contract with the U.S. Department of Health and Human Services, Health Resources and Services Administration, Division of Transplantation by the United Network for Organ Sharing (UNOS). The OPTN brings together medical professionals, transplant recipients and donor families to develop organ transplantation policy.