Delays in Prior Living Kidney Donors Receiving Priority on the Transplant Waiting List

Transcription

1 CJASN epress. Published on September 2, 2016 as doi: /CJN Article Delays in Prior Living Kidney Donors Receiving Priority on the Transplant Waiting List Jennifer L. Wainright,* David K. Klassen, Anna Y. Kucheryavaya,* and Darren E. Stewart* Abstract Background and objectives Prior living donors (PLDs) receive very high priority on the Organ Procurement and Transplantation Network (OPTN) kidney waiting list. Program delays in adding PLDs to the waiting list, setting their status to active, and submitting requests for PLD priority can affect timely access to transplantation. Design, setting, participants, & measurements We used the OPTN and the Centers for Medicare and Medicaid Services data to examine timing of (1) listing relative to start of dialysis, (2) activation on the waiting list, and (3) requests for PLD priority relative to listing date. There were 210 PLDs (221 registrations) added to the OPTN kidney waiting list between January 1, 2010 and July 31, Results As of September 4, 2015, 167 of the 210 PLDs received deceased donor transplants, six received living donor transplants, two died, five were too sick to transplant, and 29 were still waiting. Median waiting time to deceased donor transplant for PLDs was 98 days. Only 40.7% of 221 PLD registrations (n=90) were listed before they began dialysis; 68.3% were in inactive status for,90 days, 17.6% were in inactive status for days, 8.6% were in inactive status for 1 2 years, and 5.4% were in inactive status for.2 years. Median time of PLDs waiting in active status before receiving PLD priority was 2 days (range =0 1450); 67.4% of PLDs received PLD priority within 7 days after activation, but 15.4% waited 8 30 days, 8.1% waited 1 3 months, 4.1% waited 3 12 months, and 5.0% waited.1 year in active status for PLD priority. After receiving priority, most were transplanted quickly. Median time in active status with PLD priority before deceased donor transplant was 23 days. *Research Department and Office of the Chief Medical Officer, United Network for Organ Sharing, Richmond, Virginia Correspondence: Dr. Jennifer L. Wainright, United Network for Organ Sharing Research Department, 700 4th Street North, Richmond, VA jennifer. wainright@unos.org Conclusions Fewer than one half of listed PLDs were listed before starting dialysis. Most listed PLDs are immediately set to active status and receive PLD priority quickly, but a substantial number spends time in active status without PLD priority or a large amount of time in inactive status, which affects access to timely transplants. Clin J Am Soc Nephrol 11: ccc ccc, doi: /CJN Introduction Although living kidney donation is generally considered to be safe, living kidney donors (LKDs) are subject to the risk of complications (1 5) and a small risk of perioperative mortality (6,7). They also have an increased relative risk of developing ESRD after donation. LKDs rates of ESRD compare favorably with those of the general population (8) but show an increase in risk over nondonors matched on important demographic and predonation health criteria (9,10). Although development of ESRD is a relatively rare event among LKDs, the number of prior living donors (PLDs) who subsequently needed a kidney transplant is not negligible. About PLDs are added to the Organ Procurement and Transplantation Network (OPTN) kidney waiting list each year (Figure 1), for a total of 422 PLDs between September 2, 1996 and July 31, 2015 (465 registrations, including 16 multiple registrations and 27 relistings). Given that.130,000 LKDs have donated over the past several decades and the increasing length of time since the earliest donors donated, it is unsurprising that the number of PLDs added to the waiting list each year has increased over time. Recent findings on increased ESRD risk for LKDs have heightened interest in PLDs access to kidney transplantation. The transplant community s efforts to ensure appropriate waiting list access for PLDs in need of transplant, however, predate these developments. PLDs began receiving priority (regardless of waiting time) over most other local candidates on the OPTN kidney waiting list in September of 1996, and PLDs are allowed to receive this priority more than once if needed. To receive kidney offers through PLD priority, a PLD s transplant program must request priority by submitting a request to the United Network for Organ Sharing (UNOS) Organ Center. Recent work has shown that PLDs priority on the waiting list is serving them well, with waiting times notably shorter than those of comparable non PLD candidates (11,12). Muzaale et al. (11) and Potluri et al. (12) found median waiting times of 2.8 months and 145 days to deceased donor kidney transplant, respectively. These waiting times include both active and inactive time and thus, reflect the PLDs actual experience on the waiting list. Although existing research suggests that the priority system is working well for PLDs in need of transplant, Vol 11 November, 2016 Copyright 2016 by the American Society of Nephrology 1

2 2 Clinical Journal of the American Society of Nephrology Figure 1. Prior living kidney donors added to the Organ Procurement and Transplantation Network (OPTN) kidney waiting list by year of listing: January 1, 1997 to December 31, there are numerous factors that affect how rapidly a PLD receives a deceased donor kidney transplant. The most important factor is whether the PLD is added to the waiting list soon after diagnosis. Prompt listing allows the possibility of preemptive transplant, which spares the donor the physical and lifestyle burdens of dialysis. After a PLD has been approved for transplant and added to the waiting list, the next factor that affects speed of transplantation is setting the candidate s waiting list status to active. PLD candidates may be placed in inactive status for a variety of reasons, only some of which are within the control of the transplant program. Possible reasons for inactive status include incomplete workup and the candidate temporarily being too sick. Although a PLD still accrues waiting time in inactive status, waiting time is not the primary determinant of time to transplantation for PLDs because of their elevated priority, and they cannot receive organ offers unless in active status. Another factor that determines how quickly a PLD receives a transplant is the timeliness of the transplant program srequest for PLD priority. Until the program submits the request, a PLD who is listed in active status may receive organ offers but will not have PLD priority. In practical terms, this means that the PLD will appear on match runs interspersed with all other kidney candidates, many of whom will have far more waiting time than a PLD recently added to the waiting list. As soon as PLD priority is processed, the PLD may begin receiving organ offers through their PLD priority. The purpose of this study was to characterize the timeliness of PLDs listing and activation on the waiting list and programs request for PLD priority status, as well as examine patient characteristics that are associated with delays in any of these events. This is the first study exploring delays in requests for PLD waiting list priority. Materials and Methods This study used data from the OPTN. The OPTN data system includes data on all donors, waitlisted candidates, and transplant recipients in the United States submitted by the members of the OPTN and has been described elsewhere. The Health Resources and Services Administration (HRSA), US Department of Health and Human Services provides oversight to the activities of the OPTN contractor. Our cohort included all PLDs who were added to the kidney waiting list and received PLD priority between January 1, 2010 and July 31, 2015 in the United States as reported to the OPTN. This cohort excluded any PLDs who developed ESRD but were not listed for transplant, or who were listed but never received PLD priority. We determined active waiting list status of kidney candidates and time in active status without PLD priority using the OPTN waiting list audit data, which track changes in a candidate s waiting list status over time. We assessed time from the start of chronic maintenance dialysis to listing using dialysis dates from Centers for Medicare and Medicaid Services Form 2728 and the OPTN waiting list. We calculated Kaplan Meier median waiting times two different ways: (1) to reflect PLD experience (i.e., including time in inactive status or without PLD priority) and (2) to reflect time spent on the waiting list with allocation priority (i.e., excluding time spent in inactive status or without PLD priority). We used logistic regression to estimate the independent effects of patient covariates on three response variables: timing of listing, timing of active status, and timing of PLD priority. Generalized estimating equations were used in the regression analyses to account for possible center effects (clustering because of some PLDs being listed by the same center). It was hypothesized that the following variables potentially affect timing of listing, activation, and PLD priority: sex, age at listing, race/ethnicity, calculated panel reactive antibody, region, blood type, diagnosis, and the transplant center waiting list volume. To avoid model overfitting because of small sample sizes, not all covariates could be included, and additional covariates could not be explored. The clinical and research activities being reported are consistent with the Principles of the Declaration of Istanbul

3 Clin J Am Soc Nephrol 11: ccc ccc, November, 2016 Prior Living Donor Priority, Wainwright et al. 3 as outlined in the Declaration of Istanbul on Organ Trafficking and Transplant Tourism. Institutional review board exemption was obtained from the US Department of Health and Human Services HRSA. Results There were 210 transplant candidates (221 registrations) with PLD priority who were added to the kidney waiting list between January 1, 2010 and July 31, 2015 (Table 1): 38.1% of these PLDs were women, 44.3% of PLDs were white, 38.1% were black, 11.0% were Hispanic, 2.9% were Asian, 2.4% were Native American, and 1.4% were other or multiracial. Of these PLDs, 1.0% were first listed at ages years old, 25.7% were first listed between 31 and 50 years old, 63.3% Table 1. Characteristics of prior living kidney donors added to the Organ Procurement and Transplantation Network kidney waiting list between January 1, 2010 and July 31, 2015 Characteristic n=210 PLD Candidates Sex Women 80 (38.1%) Men 130 (61.9%) Ethnicity/race White 93 (44.3%) Black 80 (38.1%) Hispanic 23 (11.0%) Asian 6 (2.9%) American Indian/ 5(2.4%) Native American Multiracial 3 (1.4%) Age at listing, yr Mean (SD) 56.7 (10.5) Median (IQR) 57.5 ( ) Range CPRA (73.8%) (19.1%) (3.3%) (3.8%) Primary diagnosis Hypertensive nephrosclerosis 65 (31.0%) Diabetes mellitus 44 (21.0%) GN 6 (2.9%) Retransplant/graft failure 5 (2.4%) Other 90 (42.9%) ABO A 42 (20.0%) B 2 (1.0%) AB 30 (14.3%) O 136 (64.8%) Preemptive at listing (not on 85 (40.5%) dialysis) Days on dialysis before listing (excluding preemptive listings) Mean (SD) (838.1) Median (IQR) 332 ( ) Range PLD, prior living donor; IQR, interquartile range; CPRA, calculated panel reactive antibody; ABO, blood type. were first listed between 51 and 70 years old, and 10.0% were first listed at 71 years old or older at listing. As of September 4, 2015, 167 of the 210 PLDs received deceased donor transplants, six received living donor transplants, two died, five were too sick to transplant, and 29 were still waiting. Several PLDs received more than one transplant or were relisted for a second transplant. Kaplan Meier median waiting time to deceased donor transplant, including time spent inactive or without PLD priority, was 98 days (95% confidence interval, 78 to 141). Prompt Listing Of 221 PLD registrations, 40.7% (n=90) were added to the kidney waiting list before they began regular maintenance dialysis, and just six of these preemptively listed PLDs began dialysis after listing. Of the 131 PLD registrations (59.3%) that were not preemptive, the median time between dialysis and listing was 332 days (range = days); 6.8% of PLD registrations were listed within 3 months of the initiation of dialysis, 25.3% of PLD registrations were listed between 3 and 12 months, 12.2% of PLD registrations were listed between 1 and 2 years, and 14.9% of PLD registrations were listed.2 years after initiation of dialysis (Figure 2). Multivariable modeling revealed no associations between timing of listing (preemptive versus after initiation of dialysis) and patient and center characteristics (Table 2). Active Status The median time spent in inactive status on the waiting list was 3 days (range = days); 68.3% of PLDs were in inactive status for,90 days, 17.6% of PLDs were in inactive status for days, 8.6% of PLDs were in inactive status for 1 2 years, and 5.4% of PLDs were in inactive status for.2 years (Figure 3). Of the 31 PLD registrations (14.0%) who were in inactive status.1 year, 21 were inactive because of incomplete workup, two were inactive because of candidate choice, two were inactive because of being temporarily too well, one was inactive because of insurance issues, one was inactive because of being temporarily too sick, two were inactive because of incomplete workup plus being temporarily too sick, one was inactive because of incomplete workup plus insurance issues, and one was inactive because of inappropriate weight and medical noncompliance. Multivariable modeling revealed no associations between time in inactive status (.1 versus#1 year) and patient and center characteristics (Table 2). PLD Priority The median time for actively waiting PLDs before receiving their PLD priority was 2 days (range = days); 67.4% of PLDs received PLD priority within 7 days after activation, but 15.4% of PLDs waited 8 30 days, 8.1% waited 1 3 months, 4.1% waited 3 12 months, and 5.0% waited in active status.1 yearforpldpriority (Figure 4). Also, 25% of black PLD registrations were in active status.30 days before receiving PLD priority versus 12.4% of nonblack registrations, and this association was statistically significant (P=0.04) in multivariable modeling (Table 2). After PLDs received their PLD priority, most were transplanted quickly. The Kaplan Meier median waiting time spent in active status with PLD priority (i.e., excluding all

4 4 Clinical Journal of the American Society of Nephrology Figure 2. Time between initiation of maintenance dialysis and addition to the Organ Procurement and Transplantation Network kidney waiting list for prior living kidney donor registrations added to the waiting list January 1, 2010 to July 31, 2015 (n=221). time in inactive status or without PLD priority) before deceased donor transplant was 23 days (95% confidence interval, 20 to 30). Discussion In this study, some PLDs who were in need of kidney transplant experienced delays in access to transplantation because of delays in (1) being added to the kidney waiting list, (2) being listed in active status, and (3) receiving PLD priority. Many PLDs are exposed to months or years on dialysis before being added to the waiting list, with only 40.7% of registrations occurring before initiation of maintenance dialysis, and one half of PLDs who do not receive preemptive transplants are on dialysis for 332 days or longer before listing. Given that waiting time and time on dialysis are not major determinants of organ offers for PLDs, this practice exposes PLDs to potentially avoidable time on dialysis. After listing, most PLDs are put in active status in a timely manner, but a substantial number (14.0%) remains ineligible to receive organ offers because of inactive status for.1 year. There are valid medical and other reasons why a candidate could be kept in inactive status; it is impossible to ascertain whether programs update a candidate s inactive reasons if those reasons change during a candidate s time in inactive status, but transplant programs should work to minimize inactive time to the extent possible. A notable proportion of PLDs (17.2%) is spending 1 month or longer in active status without PLD priority, which denies these PLDs the high priority entitled to them by OPTN policy. After listed, set to active status, and awarded priority, PLDs are transplanted very rapidly (median of 23 days), and recently published research has shown that PLDs access to rapid transplantation has been maintained after implementation of the new Kidney Allocation System (13). The OPTN Board recognized the critical contribution of living donors in 1996 when it approved policy that granted PLDs priority access on the OPTN kidney waiting list. OPTN policy requires transplant programs to inform living donors of this priority as part of their predonation informed consent, and delays in providing PLD priority may undermine trust in the system. Program delays in these requests result in unnecessary delays in access to transplantation for PLDs. Given transplant programs responsibility to provide the best possible care for their candidates and the transplant community s responsibility Table 2. Multivariable logistic regression models evaluating patient and hospital characteristics associated with prior living kidney donor outcomes Odds Ratio (95% CI) Risk Factor Listing after Initiation of Maintenance Dialysis, n=131 Yes and n=90 No Inactive Time.1 yr, n=31 Yes and n=190 No Active without PLD Priority.30 d, n=38 Yes and n=183 No Race, black versus nonblack 1.31 (0.70 to 2.42) 1.14 (0.49 to 2.64) 2.31 (1.05 to 5.08) a Sex, women versus men 0.81 (0.44 to 1.50) 1.25 (0.53 to 2.92) 1.40 (0.63 to 3.14) Age at listing per 1 yr 1.01 (0.98 to 1.04) 0.97 (0.93 to 1.00) 1.00 (0.96 to 1.03) CPRA, 80% 100% versus 0% 79% 2.59 (0.67 to 9.94) 0.67 (0.10 to 4.23) 1.81 (0.47 to 7.04) Center waiting list volume per 100 additional patients 0.99 (0.96 to 1.02) 1.04 (1.00 to 1.08) 1.02 (0.98 to 1.06) P value.0.05 unless otherwise indicated. 95% CI, 95% confidence interval; PLD, prior living donor; CPRA, calculated panel reactive antibody at 4 weeks (or removal if before 4 weeks). a P=0.04.

5 Clin J Am Soc Nephrol 11: ccc ccc, November, 2016 Prior Living Donor Priority, Wainwright et al. 5 Figure 3. Time in inactive status on the Organ Procurement and Transplantation Network kidney waiting list for prior living kidney donor registrations added to the waiting list January 1, 2010 to July 31, 2015 (n=221). to promote the wellbeing of living donors (14), these delays are unacceptable. Some PLDs may choose to forgo a possible deceased donor transplant in favor of solely pursuing a living donor transplant, but no PLD should be on the waiting list in active status but without PLD priority for longer than the time necessary for the program to contact the UNOS Organ Center to request priority. The Organ Center fulfills PLD priority requests within 1 business day. Transplant programs should ensure that their staff understands the OPTN policy on PLD priority and the process to obtain priority for the program s PLD candidates. Transplant programs may contact the UNOS Organ Center with questions. Because some PLDs were waiting in active status on the kidney waiting list without PLD priority, the OPTN implemented a new process in May of 2015 to identify as many of these PLDs as possible and make their respective transplant programs aware of the situation. UNOS now regularly links the current OPTN kidney waiting list with the OPTN s list of all known living donors in the United States who donated on or after October 1, The OPTN proactively contacts programs with candidates who seem to have a match on the living donor list so that they can determine if the candidate truly is a PLD and if so, request PLD priority for the candidate. Because the OPTN does not possess living donor data for all donors and because database linkages are not always successful, some PLDs cannot be identified through this process. As a result, programs should implement their own processes to identify all PLDs among their candidates and promptly request priority. Transplant programs also should consider their protocols for preemptively listing and transplanting PLD candidates. PLD priority is a far more important determinant of organ offers for PLD candidates than waiting time and time on dialysis, and a PLD who is listed preemptively is likely to receive a transplant before dialysis is required. Although some PLDs may choose to postpone being added to the waiting list, transplant programs should ensure that PLDs who present at their program are aware of the benefits of preemptive transplantation and the ability of most PLDs to receive a transplant quickly. Programs should consider that some PLDs, such as those who are highly sensitized, may face a long wait for a kidney even with PLD priority. Such PLDs could be especially good candidates for preemptive listing. For PLDs who do need dialysis, education of dialysis providers about the transplant priority that PLDs should receive could be beneficial to PLDs under their care. Previous research on outcomes for PLDs on the waiting list has measured time to transplant using all of a candidate s Figure 4. Time in active status without prior living donor priority for prior living kidney donor registrations on the Organ Procurement and Transplantation Network kidney waiting list added to the waiting list January 1, 2010 to July 31, 2015 (n=221).

6 6 Clinical Journal of the American Society of Nephrology waiting time, including time in inactive status and time in active status without PLD priority. This assessment of actual waiting time accurately portrays the experience of PLDs after listing. It does not, however, accurately portray the true speed of the allocation system experienced by PLDs who are added to the waiting list in active status with PLD priority in a timely manner, because their waiting times are much shorter. Both clinicians and researchers should be aware of this distinction when interpreting PLD waiting times for clinical and research purposes. One limitation of this study was our inability to identify PLDs added to the waiting list for whom PLD priority was never requested. As a result of this limitation, we are unable to accurately assess the full extent of the problem, because it is possible that additional PLDs were listed without ever receiving PLD priority. Because the ability to identify PLDs on the waiting list varies according to certain demographic characteristics (e.g., a PLD who is a woman is more likely to change her last name, and a foreign national PLD is less likely to have a Social Security Number in the donor record), analyses of demographic characteristics of PLDs on the waiting list must be interpreted with caution. Another limitation of this study is the small sample size, which portends low statistical power for identifying factors significantly associated with delays in listing, active status, and PLD priority. However, we did find that black PLDs were more likely than nonblack PLDs to spend 1 month or longer in active status without PLD priority. Although this finding is statistically significant (P=0.04), it should be interpreted cautiously because it is the result of performing multiple hypotheses tests simultaneously, which can lead to false positives. Additional data are needed to confirm its validity. Still, a potential disparity associated with ethnicity is highly concerning, and although it is unlikely that this difference is on the basis of intentional discrimination, black PLDs may have less access to information about their right to PLD priority. The inclusion of this right in the recent OPTN policy requirements for the informed consent of living donors may remedy this difference in the future. In conclusion, most PLDs are listed in active status and receive PLD priority in a timely manner, but a substantial number of PLDs are spending time in active status without PLD priority or a large amount of time in inactive status, which affects their access to timely transplants. Additionally, many PLDs are exposed to months or years on dialysis before being added to the waiting list. After PLDs are listed in active status with PLD priority, most are transplanted quickly. Increased awareness among transplant programs of the benefit of timely listing and the process for quickly obtaining PLD priority is needed. Researchers also must consider this issue to properly interpret PLD waiting times after listing. Acknowledgments This work was conducted under Organ Procurement and Transplantation Network (OPTN) contract C. Preliminary results were presented as a poster at the American Society of Transplant Surgeons 16th Annual State of the Art Winter Symposium, Miami Beach, FL, and at the 2016 American Transplant Congress, Boston, MA. As a United States government sponsored work, there are no restrictions on its use. The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the OPTN. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the OPTN or the United States government. Disclosures None. References 1. 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