Wait List Management. John J. Friedewald, Darshika Chhabra, and Baris Ata. The US Transplant System. National Wait List

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1 Wait List Management John J. Friedewald, Darshika Chhabra, and Baris Ata 4 Abbreviations CDC Centers for Disease Control and Prevention CPRAs Calculated panel reactive antibodies DCD Donation after cardiac death DSA Donor service area ECD Expanded criteria donors egfr Estimated glomerular filtration rate EPTS Estimated posttransplant survival HLA Human leukocyte antigen KDPI Kidney donor profile index MPSC Membership and Professional Standards Committee NOTA National Organ Transplant Act OPO Organ procurement organization OPTN Organ Procurement and Transplantation Network PRA Panel reactive antibodies PSR Program-specific reports SCD Standard criteria donor SRTR Scientific Registry of Transplant Recipients UNOS United Network for Organ Sharing WIP Work-in-progress J. J. Friedewald, M.D. (*) Northwestern University Feinberg School of Medicine, 676 N. St. Clair, Arkes Pavilion 1900, Chicago, IL 60611, USA jfriedew@nmh.org D. Chhabra, M.D., M.P.H. Kidney Transplant Program, Advocate Christ Medical Center, Department of Medicine, Section of Nephrology, University of Illinois at Chicago, 4400 W 95th Street, Suite 112, Oak Lawn, IL 60453, USA darshika.chhabra@advocatehealth.com B. Ata Booth School of Business, The University of Chicago, 5807 South Woodlawn Ave, Chicago, IL 60637, USA Baris.Ata@chicagobooth.edu Background The US Transplant System The transplant system consists of a large network of transplant centers, organ procurement organizations (OPO), and donor hospitals. The Organ Procurement and Transplantation Network (OPTN) is the unified transplant network established by the US Congress under the National Organ Transplant Act (NOTA) of The OPTN links all professionals involved in organ donation and transplantation. United Network for Organ Sharing (UNOS), a private nonprofit organization, administers the OPTN under contract with the Health Resources and Services Administration of the US Department of Health and Human Services. Every transplant center and OPO is a member of UNOS. For ease of administration, UNOS has established 11 geographic regions that are further subdivided into local donor service areas (DSAs). National Wait List Transplant candidates waiting for a kidney transplant from a deceased donor are registered on a national transplant waiting list. UNOS maintains this list in the United States and matches donors to recipients. Each transplant center s waiting list is part of this national list. In 2011, 35,013 new registrations were added to the list (based on OPTN data as of September 11, 2012). This list encompasses patients who are both active and inactive (Status 7). Inactive patients consist of candidates who are temporarily unable to receive a transplant due to medical, social, or other conditions. During this period, patients do accrue waiting time; however, only the active patients are allocated organs. Most of the explosive growth in the waiting list has been among candidates listed as inactive, as shown in Fig M.R. Weir and E.V. Lerma (eds.), Kidney Transplantation: Practical Guide to Management, DOI / _4, Springer Science+Business Media New York

2 42 J.J. Friedewald et al. Fig. 4.1 United Network for Organ Sharing national kidney wait list additions and composition by active status Facts and Figures Sinc e UNOS beg a n ke e p i n g r e cords in 1987, over 500,000 organ transplants have been performed in the United States. More than 28,000 recipients receive lifesaving organ transplants each year. As of early June 2012, over 92,000 patients were registered with UNOS on the kidney transplant wait list. In 2011, 16,814 kidney transplants were performed, which included 11,043 from deceased donors (based on OPTN data as of May 25, 2012). Wait Times Because deceased donor kidney allocation is prioritized locally, the median wait time for kidney transplant varies across the country (Fig. 4.2 ) [ 1 ]. Efforts to equalize wait time across geographic regions have been met with both logistical and political resistance. The median wait time in 2009 was 2.3 years [ 1 ]. This varies by blood type, with blood groups O and B patients waiting the longest (5 and 6 years, respectively) compared to 1 and 3 years for blood types AB and A, respectively [ 2 ]. Wait time for Caucasians is about 40 % less than other races. Sensitized patients (i.e., patients who have anti-hla antibodies as a result of blood transfusions, pregnancy, or prior transplants) may wait longer than patients who have low level of antibodies (PRA or panel reactive antibodies). Kidney Allocation Kidneys are allocated on a local, regional, and national level. When possible, kidneys are offered locally first to minimize organ preservation time, which is associated with better graft survival. The exception is sensitized recipients of zero human Fig. 4.2 Unadjusted median wait times in years for adults transplanted in 2009, by state of transplant center [ 1 ] leukocyte antigen (HLA)-mismatched kidneys who are given priority to these close biological matches. Blood type, HLA matching, degree of sensitization, pediatric recipients, and time waiting on the list are factors taken into account in UNOS computer-based network for allocating donated organs. Every organ sharing institution is electronically linked via this secure, real-time environment over the internet so that donated organs can be placed as efficiently and as quickly as possible. Point System for Kidney Allocation The 1984 NOTA mandates that organ allocation take into account both efficiency (graft and patient survival) and equity (fair distribution) [ 3 ]. The allocation system was designed to balance fairness with medical utility and improved organ survival. Potential recipients receive one

3 4 Wait List Management point for each year they wait on the list. A few regions that have an approved variance in allocation define wait time as the time since initiating dialysis. Extra points are awarded to patients who are broadly sensitized (more than 80 % panel reactive antibody level and a negative crossmatch) and to pediatric patients. The system also includes points for better HLA-DR-matched recipients to promote longer graft survival, thereby promoting improved organ utility. Listing Practices Potential recipients undergo an evaluation to determine their candidacy for kidney transplantation and once listed, they may be required to undergo periodic testing. The evaluation process strives to identify patients who may benefit the most from transplantation, separating them from patients who may be placed at risk. Policies may vary between transplant centers within a region and across the country. Listing practices take into account median wait times and allocation variances within the region, as well as list size, while optimizing resource utilization. Some centers perform an intensive evaluation up front, which may delay time to listing. Others prefer to list with minimal or no workup and complete the evaluation later. For example, cardiac workup for low- or moderate-risk candidates at initial listing may not be required in an OPO with lengthy median wait times. However, this depends on predictability within the OPO and does not take into account zero antigen mismatch offers. Acceptance Criteria Acceptance criteria at a given transplant center will vary based on a number of factors and are often subjective. The risk tolerance of the transplant center and clinicians is an important factor here. This is also one of the major system points where patient preference comes into play. Of particular relevance are ECD and CDC increased-risk organs. Because the transplant center must convey a relative risk to a potential recipient when making the offer, acceptance often depends on how the information is conveyed and in what context. As an example, for a very highly sensitized candidate, a CDC increased-risk donor organ with which they are compatible often represents their best chance at improving their overall survival compared to staying on maintenance dialysis. Informed consent is critical in these instances and quite challenging when taking into account levels of literacy and numeracy in candidates trying to grasp concepts that often challenge transplant professionals. Developing and periodically updating protocols for guidance can help keep acceptance patterns in line with the overall goals of the transplant center. 43 Acceptance criteria can also be affected by external factors. Transplant centers are monitored on their performance, specifically short-term patient and graft survival. Programspecific reports (PSRs) are generated by the Scientific Registry of Transplant Recipients (SRTR) and reviewed by the Membership and Professional Standards Committee (MPSC) of UNOS. The PSRs are publically available and have been used by insurance providers, the lay press, and the general public to evaluate transplant center performance. There is ongoing debate about the accuracy of the formulae used to generate a center s expected outcomes, and there are initiatives at UNOS and the SRTR to improve on the methods of patient risk stratification that inform the PSRs. But currently, there is a very real disincentive for transplant centers to use high-risk organs. Poor short-term outcomes are not just harmful to patients but also can jeopardize the viability of a transplant center. The deceased donor transplant system in the United States is plagued by a high rate of discarded organs, and beyond inefficiencies in the distribution system, many blame this institutional risk aversion for high discard rates. With so many candidates dying on the wait list, improving organ acceptance and utilization rates remains a vital task. Lists Within the List Centers may manage subgroups of patients within their list differently, e.g., patients consenting to expanded criteria donors (ECD), donation after cardiac death (DCD), and Centers for Disease Control and Prevention (CDC) increasedrisk donors (donors exhibiting a behavior placing them at increased risk for HIV, hepatitis B and C). Patients with a lower life expectancy can anticipate a lesser absolute gain in life-years from transplantation. Mortality on the wait list has been reported to be around 6 % per year, as much as 10 % per year for diabetic patients, increasing with older age [ 4 ]. More effort and cost may be required to maintain older candidates with multiple comorbidities on the list. All these are factored into the complex algorithm of a center s listing, wait list maintenance, and acceptance criteria. ECD Listing Variability An extended criteria donor (ECD) kidney is a kidney from a deceased donor older than 60 years or between 50 and 59 years with any two of the following risk factors: history of hypertension, death from a cerebrovascular accident, or a terminal serum creatinine more than 1.5 mg/dl. Only patients who have previously consented to ECD kidneys are offered them. These kidneys are allocated based on wait time alone to increase predictability of which candidates will be at the top of

4 44 J.J. Friedewald et al. Fig. 4.3 Variability in extended criteria donor (ECD) listing by center [ 9 ] the list. Compared to standard criteria donor (SCD) kidneys, ECD kidneys carry the benefit of a shorter wait time. Although these organs have a 1.7-fold or higher risk of graft loss compared with SCD organs [ 5 ], they still provide a survival advantage over maintenance dialysis [ 6 ]. It is critical to allocate these organs to patients who would most benefit from them, i.e., older adults, diabetics, and patients at centers with long waiting times [ 7 ]. Generally, younger patients stand to benefit more by waiting for an SCD kidney compared to older patients [ 8 ]. An exception to this may be an elderly patient who is in a region with relatively short wait times where it may be in their interest to wait longer for a higher quality organ. ECD listing practices vary significantly across the United States due to variation in risk tolerance, adherence to evidence-based practice, and the complexity involved (Fig. 4.3 ) [ 9 ]. Sensitized Patients Sensitized patients (i.e., patients who have anti-hla antibodies as a result of blood transfusions, pregnancy, or prior transplants) may wait twice as long as patients who have low level of PRA, as they are more likely to have positive crossmatch results. The virtual crossmatch or calculated PRA (CPRA) test identifies specific donor HLA antigens in the wait-listed recipient, and these are reported to UNOS if it is determined that they are likely to engender a positive crossmatch. To avoid unnecessary testing, expense, and loss of time, highly sensitized patients are not included in a match run if the donor possesses antigens against which the recipient has preformed antibody (virtual crossmatch), thereby increasing the probability of a negative final crossmatch.

5 4 Wait List Management Timing of Transplantation Preemptive Transplants (Just-in-Time Theory) There are numerous advantages to preemptive kidney transplantation (transplantation before dialysis) including a survival advantage [ 10 ]. However, there are concerns that preemptive transplantation performed too soon (at higher levels of estimated glomerular filtration rates, egfr) may not translate into an added benefit to the recipients. Achieving just-in-time kidney transplantation with living donors is a challenge and more so with deceased donors. A candidate may be placed on the wait list and accrue points for waiting time once the egfr is below 20 ml/min/1.73 m 2. The ability to receive a preemptive kidney transplant often hinges on early listing for transplant and local waiting times. Reevaluation As wa i t time for d e c e a s e d d o n o r organs continues to increase, the complexity of managing candidates for long periods of time on the wait list increases. This is coupled with an everaging pool of candidates that have more medical comorbidities. As an example, an elderly, diabetic candidate may need cardiac clearance prior to a transplant surgery event. However, with several years to wait, when does a transplant center perform this testing? And how often should it be repeated? These answers have implications for cost, transplant center staffing, patient convenience, and even patient safety when considering invasive testing. Different strategies evolve at individual transplant centers based on their milieu, including median wait time and candidate characteristics. One effective strategy at our center has been to generate a list of candidates nearing the top of each blood group on the wait list. Those patients are brought into a clinic for an examination and to order updated tests. Then, when an offer is made, the transplant team has recent knowledge of the health and readiness of that candidate. Communication with the referring nephrologist or other provider is also more important than ever. With so many candidates inactive on the list, keeping their status accurate and managing intercurrent medical events can consume a large amount of time and resources for transplant center staff. Multiple Listing Without the prospect of a living donor, many candidates list in multiple DSAs to decrease their waiting time for transplant. 45 Multiple listing requires the ability to travel and navigate the health care system, and so is not a reality for many patients. However, given the difficult and wide geographic disparities, multiple listing is still a good option for patients that are able to do so. New Allocation System UNOS has been involved in a long and comprehensive review of the kidney allocation process. Substantial resources have been applied to improving the current system. Unfortunately, over the last three decades, a disproportionate emphasis has been placed on wait time in the allocation of kidneys based simply on the massive growth of the list (Fig. 4.4 ). The proposed new system (still not approved at the time of writing this chapter) would strive to maintain access for all candidates, while trying to maximize outcomes from each kidney. To do this, a continuous scale, the kidney donor profile index (KDPI), will be used to replace the older, binary SCD/ECD classification of kidneys. The KPDI takes into account ten donor variables that better predict the relative risk of graft failure. The top 20 % of kidneys based on KDPI will be allocated first (but not exclusively) to candidates with the longest estimated posttransplant survival (EPTS). The EPTS is calculated based on four factors: age, time on dialysis, presence of diabetes, and previous transplant status. By allocating long lasting kidneys to the longest living candidates, we can realize many more graft years of life that are lost when recipients die with a functioning graft. This in turn will also decrease candidates returning to the wait list after graft failure, thus increasing transplant opportunities for others on the list. Candidates will continue to be rank ordered as they are currently based on waiting time, CPRA points (with a sliding scale of points for increasing CPRA), and HLA-DR matching. Principles of Inventory Management and Applications to the Wait List The workings of the transplant waiting list exhibits important similarities to that of the work-in-progress (WIP) inventory at a manufacturing plant. Therefore, the same core principles can guide the management of both. Managing the WIP inventory at a manufacturing plant aims at matching supply and demand, trying to eliminate any mismatch between the two. In the transplant system, the supply of organs is significantly lower than the demand for them. The objective is to reduce this imbalance and match the supply and demand, as in the case of manufacturing.

6 46 J.J. Friedewald et al. Fig. 4.4 Number of kidney transplant candidates on the waiting list and number of transplants performed per year A key metric widely used in the inventory management literature is the inventory turns (11). Following that literature, an analogous metric for managing the transplant wait list is the patient-inventory turns defined as Patient-inventory turns = Effective transplant rate/number of patients on the list. The higher the turns are, the more efficient the management of the wait list becomes. A crucial aspect of the transplant wait list is that the candidates (and the organs available for transplant) are heterogeneous. Moreover, the allocation policy (i.e., UNOS point system) determines the composition of the list. Different allocation policies lead to different compositions of patient demographics on the wait list. Therefore, for a more effective wait list (or patient inventory) management, we propose a more refined metric that calculates the patient-inventory turns for each demographic (e.g., different blood types, CPRAs, age groups) separately. In that calculation, the numerator and the denominator are the number of transplants received in a year by and the average candidate inventory for that demographic, respectively. The turn numbers for the various patient groups not only identify the patient demographics suffering most on the wait list and help track the performance of various patient groups over time, but it helps assess the disparity among various demographics. Different turn numbers for different patient demographics facilitate a tailored approach, whereby patients with different demographics can benefit from different wait list management strategies. As an aside, other important performance metrics such as waiting time, wait list mortality, and percentage of patients receiving a transplant are strongly correlated with the patient-inventory turns, i.e., high turns imply low waiting times and wait list mortality and a higher percentage of patients receiving a transplant. The most effective way of increasing turns, and hence, improving performance, is to increase the effective transplant rate, which will reduce the patient inventory in the long term too. An increase in living donors certainly increases the transplant rate, but this can be achieved in several other ways, e.g., increasing the usage of ECD or DCD organs. This requires educating the candidates about such options and encouraging them to list for ECD organs, particularly given the wide disparity in ECD listing practices previously mentioned. Furthermore, such an effort can be focused more toward the candidate demographics for whom the patientinventory turns are low, because those candidates are the ones with long expected waits and high wait list mortality rates. Such a focused approach will likely reduce the implementation cost of this effort while simultaneously increasing its effectiveness. Increasing the transplant rate can also be achieved by increasing the utilization of the organs offered to the wait list (i.e., by minimizing organ wastage).

7 4 Wait List Management This, in turn, relates to the transplantability (or readiness for transplant) of patients. For example, making sure that the patients up-to-date information, fresh blood samples for crossmatching, etc. are available increases their chances of receiving a transplant. However, making sure that patients are ready for transplant at all times may be costly. Once again, the patient- inventory turns metric for the various demographics can be used to facilitate a tailored approach for different candidates. Those candidates who belong to demographic groups with high turns should be kept active at all times. In contrast, for those patients with low turns, it may be cost-effective to delay the work necessary to activate them. In the latter case, when to activate a patient can be decided by a careful comparison of the lead time of getting the candidate ready for transplant and his expected remaining time on the waiting list (if he were ready for transplant). A related consideration is that the patients information should be updated periodically, and those ineligible for transplant should be removed from the wait list. This increases the turns metric because it reduces the denominator. More importantly, it leads to a more accurate measure of performance. Summar y The number of kidney transplant candidates on the UNOS waiting list far exceeds the number of transplants performed each year. Organ allocation is a complex system, aiming at balancing efficiency and equity. The transplant community is scrutinizing the system, working toward maximizing outcomes from each organ, while maintaining access for all. Improved management of the wait list can increase opportunities for transplant for candidates while simultaneously streamlining resource utilization at transplant centers. References U S Renal Data System, USRDS 2011 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Leichtman AB, Cohen D, Keith D, O'Connor K, Goldstein M, McBride V, et al. Kidney and pancreas transplantation in the United States, : the HRSA breakthrough collaboratives and the 58 DSA Challenge. Am J Transplant. 2008;8(4 Pt 2): PubMed PMID: National Organ Transplant Act (NOTA) Danovitch GM, Cohen DJ, Weir MR, Stock PG, Bennett WM, Christensen LL, et al. Current status of kidney and pancreas transplantation in the United States, Am J Transplant. 2005;5(4 Pt 2): PubMed PMID: Port FK, Bragg-Gresham JL, Metzger RA, Dykstra DM, Gillespie BW, Young EW, et al. Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation. 2002;74(9): PubMed PMID: Ojo AO, Hanson JA, Meier-Kriesche H, Okechukwu CN, Wolfe RA, Leichtman AB, et al. Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. J Am Soc Nephrol. 2001;12(3): PubMed PMID: Merion RM, Ashby VB, Wolfe RA, Distant DA, Hulbert-Shearon TE, Metzger RA, et al. Deceased-donor characteristics and the survival benefit of kidney transplantation. JAMA. 2005;294(21): PubMed PMID: Schold JD, Meier-Kriesche HU. Which renal transplant candidates should accept marginal kidneys in exchange for a shorter waiting time on dialysis? Clin J Am Soc Nephrol. 2006;1(3): PubMed PMID: G r a m s M E, Womer KL, Ugarte RM, Desai NM, Montgomery RA, Segev DL. Listing for expanded criteria donor kidneys in older adults and those with predicted benefit. Am J Transplant. 2010;10(4): PubMed PMID: Pubmed Central PMCID: PMC Friedewald JJ, Reese PP. The kidney-first initiative: what is the current status of preemptive transplantation? Adv Chronic Kidney Dis. 2012;19(4): PubMed PMID: Pubmed Central PMCID: PMC