Kidney Waitlist Research Articles

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID‐19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (−90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (−45%), and other organs saw similar decreases: lung (−70%), heart (−43%), and liver (−37%). Deceased donors recovered dropped from 260 to 163 (−45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (−67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID‐19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation.

Molecular mismatch analysis for assessment of histocompatibility in transplantation requires high-resolution HLA typing. Algorithms to "guesstimate" high-resolution from low-resolution typing exist, but their accuracy remains unknown. We converted high-resolution, sequence-based, HLA typing of 310 subjects from an ethnically heterogeneous population to low-resolution equivalents and tested the ability of the NMDP HaploStats and HLA Matchmaker programs to impute/reproduce the measured high-resolution HLA type, using the more common "winner-takes-all" approach. Only 35.6% of the HaploStats imputed HLA-A, -B, -C, -DRB1, and -DQB1 haplotypes had no mistakes, and the accuracy was significantly lower for non-Caucasians (29.1%) compared to Caucasians (45.2%) (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.8; P=.004). HLA Matchmaker was not able to provide high-resolution haplotypes for 45.2% of Caucasian subjects and 63.5% of non-Caucasian subjects (P=.002). Of those with an imputed result, only 10.3% of Caucasians and 4.8% of non-Caucasians had accurate 10-allele high-resolution output. Eplet analysis revealed additional, inaccurate eplets in 37% of individuals, with 22.5% showing at least 2 additional, inaccurate eplets; incorrect eplets were more common among non-Caucasians (OR, 1.8; 95% CI, 1.1-2.9; P=.018). Given this high error rate, caution should be taken before using imputation tools for clinical or research purposes, especially for non-Caucasian individuals.

Difference in Survival in Early Kidney after Liver Transplantation Compared with Simultaneous Liver-Kidney Transplantation: Evaluating the Potential of the “Safety Net”

Decisions on who requires simultaneous liver-kidney (SLK) transplantation are controversial. United Network for Organ Sharing implemented a "safety net" in 2017 providing prioritization on the kidney waitlist for patients with renal failure after liver transplantation. We aimed to compare survival after early kidney after liver transplantation (KALT) and SLK. We compared SLK, KALT, and liver transplantation alone (LTA) in adult patients who underwent deceased donor (DD) liver transplantation in the US, from 2002 to 2018. Early KALT was defined as 60 to 365 days between liver and subsequent kidney transplantation (reflecting safety net listing criteria). Patients who died within 60 days were excluded to mitigate immortal time bias favoring KALT. There were 6,774 SLK, 120 KALT at 60 to 365 days, and 11,501 LTA. Early KALT had equivalent survival compared with SLK, both for all KALT (hazard ratio [HR] 0.58, 95% CI 0.34-1.00, p= 0.05) and for DD KALT only (HR 0.72, 95% CI 0.37-1.38, p= 0.32). Simultaneous liver-kidney transplantation was associated with improved survival compared with LTA (HR 0.82. 95% CI 0.76-0.87, p < 0.01). Early KALT was associated with a greater reduction in mortality compared with LTA, but this was not significant (HR 0.58, 95% CI 0.39-1.00, p= 0.05). There was a lower proportion of early KALT in African Americans relative to SLK transplantations (7% vs 16%, p= 0.04). Early KALT has equivalent survival compared with SLK transplantation, both for all KALT and for DD KALT only, supporting the promise of the "safety net." There was a lower proportion of African-American patients undergoing early KALT, indicating the importance of monitoring access to early KALT under the "safety net" policy.

Robust Multiclass Queuing Theory for Wait Time Estimation in Resource Allocation Systems

In this paper, we study systems that allocate different types of scarce resources to heterogeneous allocatees based on predetermined priority rules—the U.S. deceased-donor kidney allocation system or the public housing program. We tackle the problem of estimating the wait time of an allocatee who possesses incomplete system information with regard, for example, to his relative priority, other allocatees’ preferences, and resource availability. We model such systems as multiclass, multiserver queuing systems that are potentially unstable or in transient regime. We propose a novel robust optimization solution methodology that builds on the assignment problem. For first-come, first-served systems, our approach yields a mixed-integer programming formulation. For the important case where there is a hierarchy in the resource types, we strengthen our formulation through a drastic variable reduction and also propose a highly scalable heuristic, involving only the solution of a convex optimization problem (usually a second-order cone problem). We back the heuristic with an approximation guarantee that becomes tighter for larger problem sizes. We illustrate the generalizability of our approach by studying systems that operate under different priority rules, such as class priority. Numerical studies demonstrate that our approach outperforms simulation. We showcase how our methodology can be applied to assist patients in the U.S. deceased-donor kidney waitlist. We calibrate our model using historical data to estimate patients’ wait times based on their kidney quality preferences, blood type, location, and rank in the waitlist. This paper was accepted by Yinyu Ye, optimization.

P132 Improving pre-kidney transplantation laboratory utilization in an era of increasing waitlist size

Aim Beginning on March 25, 2015, our institution’s kidney transplant program has implemented a “readiness” protocol, whereby patients are listed after limited workup and comprehensive testing is deferred until the anticipated time to transplantation is approximately 6–12 months. Prior to implementation of this protocol, our histocompatibility laboratory would receive monthly sera for anti-HLA antibody screening immediately upon listing. However, as part of the readiness strategy, the lab now requests monthly samples only when a candidate is predicted to have 6–12 months of waitlist time remaining. The monthly samples are stored and screened in the lab per protocol (every 3 months for most patients). All candidates are also screened once prior to listing and again immediately after listing. Methods Data from our laboratory database and UNOS were analyzed to determine the number of samples received from waitlisted kidney transplant candidates and the number tested in the three-year period before and after implementation of the readiness protocol. Results Our kidney transplant waitlist has grown from 379 candidates on 7/1/2012 to 948 as of 4/5/2018. Despite this rapid growth, the number of samples received from kidney transplant candidates has decreased from 9171 during the three-year period prior to the implementation of readiness (∼3057/year) to 7924 during the subsequent three-year period (∼2641/year). Based on a sample submission rate of ∼7 samples/patient/year, an estimated 4961 samples per year would have been received without the readiness protocol, with an estimated 6669 samples expected for 2018. From 3/25/12–3/24/15, 4730 antibody screening tests on kidney waitlist candidates were performed by Luminex (∼1577 tests/year), compared to a slight increase to 5082 from 3/25/15–3/24/18 (∼1694 tests/year), despite a 2.5-fold increase in patients on the waitlist from 2012–2018. Conclusions Implementation of the readiness protocol has streamlined the pre-transplant testing process and reduced both the number of samples received and the number tested. This has allowed us to manage a greatly increased waitlist with the same level of resources and has resulted in reduced cost per patient.

Medical Management of Transplant Patients

Kidney transplant is the best form of renal replacement therapy for most end-stage kidney disease patients due to improved quality of life and superior patient survival compared to chronic maintenance dialysis. Long-term outcome of kidney allograft recipients depends on the longevity of the allograft and optimal management of their comorbidities such as cardiovascular disease risk factors. According to organ procurement and transplant data in the United States, 14.5% of the deceased donor kidney wait list comprised patients who failed their first allograft and were awaiting second kidney transplant. Optimal immunosuppression management is key to both short- and long-term outcomes of allograft transplant by preventing rejection while avoiding or minimizing risk of over immunosuppression such as with infections and neoplasia. Cardiovascular disease is the leading cause of mortality after kidney transplant. It accounts for approximately 50% of deaths in the post transplant period and 30% of deaths among patients with preserved renal allograft function. Hence, it is crucial to optimally manage cardiovascular risk factors such as hypertension and diabetes post transplant. In this chapter, we review medical management of kidney transplant recipients, including commonly used induction therapies, maintenance immunosuppressive agents, and posttransplant medical complications such as posttransplant diabetes mellitus, hypertension, cardiovascular disease, bone disease, and BK viral infection. This review contains 1 table and 47 references Key Words: kidney transplantation, immunosuppression, rejection, post transplant diabetes mellitus (PTDM), BK viral infection, calcineurin inhibitors,

Hepatitis C virus-infected kidney waitlist patients: Treat now or treat later?

Currently many but not all centers transplant hepatitis C virus (HCV) viremic positive (+) donor kidneys into HCV+ recipients. Directed donation of HCV+ organs reduces the wait time to transplantation for HCV+ patients. Direct-acting antiviral (DAA) therapy can cure HCV in virtually all who are infected. Some have suggested that treatment of HCV+ waitlisted patients be deferred with the hope that earlier transplantation will provide better outcomes than early DAA therapy. However, there are not enough organs to guarantee prompt transplantation for the current waitlist of infected candidates. A Markov medical decision analysis model was created to compare the overall outcomes of delayed DAA therapy (Option 1) to immediate DAA therapy (Option 2) in waitlisted HCV+ patients. Option 1 patients were modeled to be transplanted 1year earlier, with a higher cumulative transplant incidence (54% at 5years post-listing vs 45% for Option 2). Despite this, Option 2 provided 0.43 (95% confidence interval [CI] 0.38-0.49) more life years than Option 1. However, Option 1 was preferred for regions with much greater access to HCV+ organs or in patients with very low HCV+-associated mortality. The best option from an individual patient's perspective will differ by region and candidate.

Medical Management of Transplant Patients

Kidney transplant is the best form of renal replacement therapy for most end-stage kidney disease patients due to improved quality of life and superior patient survival compared to chronic maintenance dialysis. Long-term outcome of kidney allograft recipients depends on the longevity of the allograft and optimal management of their comorbidities such as cardiovascular disease risk factors. According to organ procurement and transplant data in the United States, 14.5% of the deceased donor kidney wait list comprised patients who failed their first allograft and were awaiting second kidney transplant. Optimal immunosuppression management is key to both short- and long-term outcomes of allograft transplant by preventing rejection while avoiding or minimizing risk of over immunosuppression such as with infections and neoplasia. Cardiovascular disease is the leading cause of mortality after kidney transplant. It accounts for approximately 50% of deaths in the post transplant period and 30% of deaths among patients with preserved renal allograft function. Hence, it is crucial to optimally manage cardiovascular risk factors such as hypertension and diabetes post transplant. In this chapter, we review medical management of kidney transplant recipients, including commonly used induction therapies, maintenance immunosuppressive agents, and posttransplant medical complications such as posttransplant diabetes mellitus, hypertension, cardiovascular disease, bone disease, and BK viral infection. This review contains 1 table and 47 references Key Words: kidney transplantation, immunosuppression, rejection, post transplant diabetes mellitus (PTDM), BK viral infection, calcineurin inhibitors,

Dynamic Incentives in Wait List Mechanisms

Many scarce public resources are allocated through wait lists that use priorities for individual agents. A new priority system for allocating deceased donor kidneys was adopted in 2014. This redesign was guided by simulations that held decision-rules fixed. We synthesize recent theoretical results to show that the welfare effects of a mechanism depend on the interaction between dynamic incentives and heterogeneity in preferences. We show evidence suggesting that patient decisions on the deceased donor kidney wait list respond to dynamic incentives. Therefore, an empirical approach to dynamic mechanism design is an essential complement to mechanism design theory in dynamic environments.

Transplantation Opportunities of Hepatitis C Virus–Seropositive Patients on the Kidney Waiting List

ObjectiveBesides severe organ shortage, hepatitis C virus (HCV) infection is an important obstacle for kidney transplantation because of long waiting times on deceased kidney donor waiting lists. We aimed to evaluate calling number of candidates according to HCV serology. MethodA total of 404 adults on the deceased donor waiting list invited for cadaveric transplantation was evaluated. Demographic data, waiting time, calling number for transplantation, and viral serology were obtained during the 6-year period. ResultsMean waiting duration and calling number of all patients were 42.7 ± 34 months and 1.56 ± 4.37 times, respectively. Twenty-six candidates had chronic HCV infection and 12 of 26 were HCV RNA–positive. Mean waiting duration and calling number in anti-HCV–positive candidates were significantly higher compared with anti-HCV–negative candidates (85.3 ± 38.8 vs 39.8 ± 31.6 months, and 10.8 ± 10.3 vs 0.92 ± 2.6 times, respectively; P < .001). Mean waiting duration and total calling number in HCV-RNA–positive candidates were significantly higher than in HCV-RNA–negative ones (107.5 ± 7.5 vs 66.2 ± 44.8 months; P = .018; 15 ± 9.7 vs 7.3 ± 9.8 times, respectively; P = .026). ConclusionsChronic HCV infection is an important issue leading to longer waiting time on the list. Our observation showed that waiting durations of anti-HCV–positive candidates were longer than that of negative patients, although they had more frequent opportunity for transplantation.

Socioeconomic Inequalities in the Kidney Transplantation Process: A Registry-Based Study in Sweden.

Few studies have examined the association between individual-level socioeconomic status and access to kidney transplantation. This study aims to investigate the association between predialysis income and education, and access to (i) the kidney waitlist (first listing), and (ii) kidney transplantation conditional on waitlist placement. Adjustment will be made for a number of medical and nonmedical factors. The Swedish Renal Register was linked to national registers for adult patients in Sweden who started dialysis during 1995 to 2013. We employed Cox proportional hazards models. Nineteen per cent of patients were placed on the waitlist. Once on the waitlist, 80% received kidney transplantation. After adjusting for covariates, patients in the highest income quintile were found to have higher access to both the waitlist (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.53-1.96) and kidney transplantation (HR, 1.33; 95% CI, 1.16-1.53) compared with patients in the lowest income quintile. Patients with higher education also had better access to the waitlist and kidney transplantation (HR, 2.16; 95% CI, 1.94-2.40; and HR, 1.16; 95% CI, 1.03-1.30, respectively) compared with patients with mandatory education. Socioeconomic status-related inequalities exist with regard to both access to the waitlist, and kidney transplantation conditional on listing. However, the former inequality is substantially larger and is therefore expected to contribute more to societal inequalities. Further studies are needed to explore the potential mechanisms and strategies to reduce these inequalities.

P133 Uncertainty is the new reality: The risk in using the virtual crossmatch as a gatekeeper to transplantation

Aim To evaluate fluctuations in HLA antibodies for kidney waitlist candidates to determine optimal screening frequency and reduce inaccuracies in virtual crossmatches assessments (VXM). Methods HLA antibodies were identified and assessed using phenotype panels (Lifecodes, Immucor) and single antigen panels (Labscreen, One Lambda). All sera were treated with hypotonic dialysis or Melon Column™ prior to testing to remove prozone interference. Results The new kidney allocation system has increased the use of VXMs to assess donor compatibility prior to acceptance of imported organs. During the month of November 2016, 111 VXMs were performed for kidney waitlist candidates; of those patients 28 (25%) had a change in their HLA antibody status over the course of their sample history. Six patients (5.4%) had an antibody increase that potentially impacted the VXM, i.e the change occurred within the three month window around the virtual assessment. Five patients had samples older than 30 days at time of VXM and upon receipt of a new sample a significant HLA antibody increase had occurred. For one patient, despite having a sample within 30 days of the VXM, there was an on going antibody increase and although the VXM was reported as flow cytometric crossmatch negative, the new reality was antibody at CDC crossmatch positive levels. Conclusions VXMs have increased most dramatically in our highly sensitized patients (>80% CPRA), accounting for 50% of the virtual crossmatches performed in our November cohort. This population was found to have a high incidence (25%) of HLA specific antibody fluctuations while on the waitlist. A 3 month screening interval was sufficient in producing accurate VXM assessments for nearly 95% of our cohort; however, accuracy was compromised for the remaining patients due to unanticipated changes between test samples. Better communication of inflammatory events that may trigger sensitization changes or preoperative testing is needed to ensure VXM accuracy, patient safety, and successful transplant outcomes. Download high-res image (208KB) Download full-size image

P010 Higher definition CPRA: What’s the (decimal) point?

Aim cPRA is an estimate of the percentage of donors excluded by a potential recipient’s unacceptable antigens and is typically expressed as an integer. For very highly sensitized patients, integer rounding may reduce how informative cPRA is for important metrics such as time to DSA negative offer. We analyzed the distribution and clinical impact of cPRA to decimal point based (cPRAd) in a highly sensitized Canadian kidney waitlist (cPRA>=95%). Methods All patients registered the Canadian Blood Services’ Highly Sensitized Patient (HSP) Program included in at least one allocation run ( n = 1025) from 10/18/13 to 08/04/16 were included and cPRAd calculated to 1 decimal place. Distribution of cPRAd, time to first DSA negative match or to end of study period and proportion of patients transplanted by cPRAd was determined. Result 52% of subjects had cPRAd>=99.8%. 515 patients received at least one DSA negative match during the study period (Fig. 1A). Time to match increased progressively across cPRAd, notable even between integer values (Fig. 1B). Median time to first match increases progressively above cPRAd 98% and particularly above 99.7%. (Fig. 1C). Noting not all matches results in offers/transplants, for those patients transplanted with cPRAd>=98%, proportion transplanted decreases across cPRAd 0.1% intervals (Fig. 2) (Linear relationship = −0.279 * (cPRAd) + 27.95, R 2 = 0.59, p = 0.00004). Conclusions cPRAd provides more informative time to match and likelihood of transplant, than rounded integer cPRA, which in turn may better inform patients, and augment application in allocation strategies. Download high-res image (458KB) Download full-size image

Complement-dependent cytotoxicity and Luminex technology for human leucocyte antigen antibody detection in kidney transplant candidates exposed to different sensitizing events.

BackgroundThe aim of this study was to determine the frequency of exposure to different sensitizing events (SEs) and to assess their effects on human leucocyte antigen (HLA) alloimmunization in transplant candidates using two different HLA antibody screening techniques: complement-dependent cytotoxicity (CDC) and Luminex.MethodsThis retrospective study included HLA antibody screening results for 163 patients on the kidney transplant waiting list (WL) tested from March 2012 until the end of December 2015 at the Tissue Typing Laboratory, Rijeka, Croatia. All sera samples were tested using the CDC and Luminex techniques in parallel.ResultsTwo-thirds of the patients [114 (70%)] on the WL were exposed to transfusions, pregnancies and/or kidney transplant. The pre-transplant sera of 104 (63.80%) patients were negative for antibodies. In the sera of 23 (14.11%) patients, HLA antibodies were detected by CDC and Luminex and in the sera of 36 (22.09%) patients by Luminex only.ConclusionIn patients on kidney WL, previous organ transplantation represents the strongest immunogenic stimulus, followed by blood transfusions (the most frequent SE) and pregnancies. Although Luminex is more sensitive than CDC in HLA antibody detection, the decision on unacceptable HLA antigens in WL patients has to be based on the results of both assays and the patient’s immunization history.

Long-term survival following kidney transplantation in previous lung transplant recipients-An analysis of the unos registry.

Kidney transplantation has been advocated as a therapeutic option in lung recipients who develop end-stage renal disease (ESRD). This analysis outlines patterns of allograft survival following kidney transplantation in previous lung recipients (KAL). Data from the UNOS lung and kidney transplantation registries (1987-2013) were cross-linked to identify lung recipients who were subsequently listed for and/or underwent kidney transplantation. Time-dependent Cox models compared the survival rates in KAL patients with those waitlisted for renal transplantation who never received kidneys. Survival analyses compared outcomes between KAL patients and risk-matched recipients of primary, kidney-only transplantation with no history of lung transplantation (KTx). A total of 270 lung recipients subsequently underwent kidney transplantation (KAL). Regression models demonstrated a lower risk of post-listing mortality for KAL patients compared with 346 lung recipients on the kidney waitlist who never received kidneys (P<.05). Comparisons between matched KAL and KTx patients demonstrated significantly increased risk of death and graft loss (P<.05), but not death-censored graft loss, for KAL patients (P=.86). KAL patients enjoy a significant survival benefit compared with waitlisted lung recipients who do not receive kidneys. However, KAL patients do poorly compared with KTx patients. Decisions about KAL transplantation must be made on a case-by-case basis considering patient and donor factors.

Access to Kidney Transplantation among HIV-Infected Waitlist Candidates.

Kidney transplantation among HIV-infected patients with ESRD confers a significant survival benefit over remaining on dialysis. Given the high mortality burden associated with dialysis, understanding access to kidney transplantation after waitlisting among HIV+ candidates is warranted. Data from the Scientific Registry of Transplant Recipients were linked to Intercontinental Marketing Statistics pharmacy fills (January 1, 2001 to October 1, 2012) so that we could identify and study 1636 HIV+ (defined as having filled one or more antiretroviral medications unique to HIV treatment) and 72,297 HIV- kidney transplantation candidates. HIV+ waiting list candidates were more often young (<50 years old: 62.7% versus 37.6%; P<0.001), were more often men (75.2% versus 59.3%; P<0.001), were more often black (73.6% versus 27.9%; P<0.001), had longer time on dialysis (years: 2.5 versus 0.8; P<0.001), were more often coinfected with hepatitis C virus (9.0% versus 3.9%; P<0.001), and were less likely to remain active on the waiting list (37.7% versus 49.4%; P<0.001). Waitlist mortality among HIV+ candidates was similar compared with HIV- candidates (adjusted hazard ratio, 1.03; 95% confidence interval, 0.89 to 1.20; P=0.67). In contrast, likelihood of living donor kidney transplantation was 47% lower (adjusted hazard ratio, 0.53; 95% confidence interval, 0.44 to 0.64; P<0.001), and there was a trend toward lower likelihood of deceased donor kidney transplantation (adjusted hazard ratio, 0.87; 95% confidence interval, 0.74 to 1.01; P=0.07) compared with in HIV- candidates. Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates.

The ASCENT (Allocation System Changes for Equity in Kidney Transplantation) Study: A Randomized Effectiveness-Implementation Study to Improve Kidney Transplant Waitlisting and Reduce Racial Disparity

IntroductionThe United Network for Organ Sharing (UNOS) implemented a new Kidney Allocation System (KAS) in December 2014 that is expected to substantially reduce racial disparities in kidney transplantation among waitlisted patients. However, not all dialysis facility clinical providers and end-stage renal disease (ESRD) patients are aware of how the policy change could improve access to transplantation.MethodsWe describe the ASCENT (Allocation System Changes for Equity in Kidney Transplantation) study, a randomized, controlled effectiveness-implementation study designed to test the effectiveness of a multicomponent intervention to improve access to the early steps of kidney transplantation among dialysis facilities across the United States. The multicomponent intervention consists of an educational webinar for dialysis medical directors, an educational video for patients and an educational video for dialysis staff, and a dialysis facility−specific transplantation performance feedback report. Materials will be developed by a multidisciplinary dissemination advisory board and will undergo formative testing in dialysis facilities across the United States.ResultsThis study is estimated to enroll ∼600 US dialysis facilities with low waitlisting in all 18 ESRD networks. The co-primary outcomes include change in waitlisting and waitlist disparity at 1 year; secondary outcomes include changes in facility medical director knowledge about KAS, staff training regarding KAS, patient education regarding transplantation, and the intent of the medical director to refer patients for transplantation evaluation.DiscussionThe results from the ASCENT study will demonstrate the feasibility and effectiveness of a multicomponent intervention designed to increase access to the deceased donor kidney waitlist and to reduce racial disparities in waitlisting.

P085 Heat map of HLA antibody profiles in 5281 kidney wait list candidates revealed locus/CREG/bead-specific patterns associated with mode of sensitization

Aim To assess the nature of HLA antibody (Ab) profile in kidney transplant (tx) candidates. Method Kidney waitlist candidates (n = 5281) were tested for 123 distinct HLA Ab using One Lambda single antigen beads on DTT-treated sera. Mean fluorescence intensity (MFI) of all detected Ab were used to generate heat map and Ab patterns were compared with several conditions. Results Figure shows the heat map of HLA Ab in sensitized patients with CPRA >20%. As expected, the Ab producers are more common in re-tx group and produce high MFI (>10 K) Ab to DQ (47% vs. 4%), DP (21% vs. 3%) and A (37% vs. 8%) antigens compared to 1st-tx group. In the re-tx group, females are frequent producers of Ab to HLA-B, C, DR and A1 and A2 CREGs, while males are frequent producers of Ab to DQ, DP and A10 CREG. High MFI (>10 K) DQ Ab producers are more common in re-tx males, which is consistent with the fact that the de novo donor-specific antibodies produced post-tx are frequently DQ-specific. In the 1st-tx candidates, females are frequent Ab producers and common Abs are directed to HLA-B, DR and A1 & A2 CREGs. The composite MFI of 1st-tx females and males have a median of 16 K and 6 K, respectively. The most frequent Abs that occur in >4% of 1st-tx males are weakly reactive (MFI DQ7 > B44 > B82 > DP1 > B45 > B57 > A66 > DP11 > A80 > Cw15. These weak Abs are also seen frequently in 1st-tx females. No association was observed between these weak reactions and candidates’ transfusion history, age, race, primary disease, blood group & HLA types, suggesting cryptic epitope reactivity of these beads. The most frequent Ab in all sensitized patients is B76 (1.5%). The most frequent Ab in sensitized patients per locus is A25 (6.4%), B76 (2.8%), Cw15 (11.5%), DR9 (9%), DQ7 (19.4%) and DP6 (7.7%). Conclusions Weak Ab detected frequently in 1st-tx males are likely directed to cryptic epitopes and require additional scrutiny including screening by another reagent. High frequency of MFI > 10 K DQ Ab in re-tx males suggest the need for DQ matched tx. Download : Download high-res image (891KB) Download : Download full-size image

P128 Transplant patients with HLA allele antibodies need donors typed at that level

We are disadvantaging pre and post transplant patients who have potential HLA allele donor specific antibodies (DSAs), when deceased donors are not typed an intermediate or high resolution. How can we estimate the antibody mediated rejection risk (AMR), when we can’t tell if an allele antibody is a DSA? With RT-PCR, SSP and rSSO, we have the ability to type donors in 3–6 h at intermediate to near allele level, why isn’t this level required, it is often needed? Forty-eight percent of my kidney waitlist active patients have HLA antibodies, seventy-eight percent of these patients have some allele antibodies. About twenty-five percent of our virtual and prospective crossmatches involve interpreting potential allele DSAs. Fortunately, Our OPO provides most organ offers with intermediate HLA typing and the typing data, which frequently has enabled an accurate identification of DSAs, and a better estimation of the risk of AMR. An example of how intermediate donor typing, with a patient’s single antigen profile can help identify DSAs:identify DSAs: Download : Download high-res image (91KB) Download : Download full-size image We need to require donor typing at near allele level, to provide pre and post transplant patients better AMR risk assessment and access to transplantation. S.S. Geier: Consultant; Company/Organization; Consulting Director LABSNE, Gift of Life OPO HLA Lab. Scientific/Medical Advisor; Company/Organization; Donor Alliance OPO Advisor Board member. Employee; Company/Organization; Temple University Hospital and Lewis Katz School of Medicine, Director Immunogenetics Lab. Other (Identify); Company/Organization; 2016 UNOS Region 2 representative to the Histo Committee.

P010 Complex constellation of HLA antibodies contributes to decreasing trend of kidney transplant rate in candidates with 100% CPRA

The key component of the new kidney allocation system is increased priority for sensitized candidates. While transplants (tx) have increased 6 fold for recipients with a CPRA of ⩾99%, the trend in tx for these patients began to decrease over the 1st year. To determine if HLA antibody composition contributes to the decreasing tx rate, we compared the distribution of Cross-REactive Groups (CREG) in our waitlist candidates with different CPRA ranges. Kidney waitlist candidates (n = 5281) were tested for HLA antibodies using One Lambda single antigen beads on DTT-treated sera. CPRA values were determined based on unacceptable antigens (UA), and were clustered into 100%, 99%, 98%, 80–97% and 20–79% CPRA groups. The number of UA differs significantly between CPRA groups (Table). The 100%-CPRA group display 18–107 UA (98% of this group display >25 UA and 72% display ⩾50 UA). The 99%-CPRA group display 13–61 UA (78% display ⩾25 UA) while the 98%-CPRA group display 8–60 UA (66% display ⩾25 UA). The incidence of CREG HLA antibodies differs significantly among CPRA groups. Most candidates with 100% CPRA display 2–3 fold increase in the number of CREGs compared to candidates with 99% or 98% CPRA. More than 3 CREGs were observed in 63.8% of the 100%-CPRA group, but only in 21.3% of the 99%-CPRA group, in 2% of the 98%-CPRA group and in 1.4% of the 80–97%-CPRA group. Candidates with CPRA <80% did not display more than 4 CREGs. Over 80% of the candidates in the 100%-CPRA group are homozygotes at multiple HLA loci, and display antibodies to all antigens of one or more HLA loci except to self. Moreover, the probability of finding HLA-A/B/DR antigen matched kidney is zero for 43.6% of the candidates with 100% CPRA. These results suggest that the majority of the candidates in the100%-CPRA group are very broadly sensitized and are hard to find a compatible kidney, and thus need an alternative approach such as desensitization and living-donor kidney exchange. These data support the importance of HLA matching at least at the level of CREG.