A Share 21 model in liver transplantation: Impact on waitlist outcomes

With the introduction of Model for End‐Stage Liver Disease‐Sodium (MELD‐Na)–based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD‐Na scores <21 and explore the utility of replacing “Share 15” with “Share 21.” The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD‐Na–based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD‐Na score of 6‐14 (Group 1) and those with a score of 15‐20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6‐14 (Group 1) and 3282 with a score of 15‐20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD‐Na scores without compromising waitlist outcomes.     

A change of heart: Preliminary results of the US 2018 adult heart allocation revision

In 2018, the Organ Procurement and Transplantation Network (OPTN) modified adult heart allocation to better stratify candidates and provide broader access to the most medically urgent candidates. We analyzed OPTN data that included waiting list and transplant characteristics, geographical distribution, and early outcomes 1 year before (pre: October 18, 2017‐October 17, 2018) and following (post: October 18, 2018‐October 17, 2019) implementation. The number of adult heart transplants increased from 2954 pre‐ to 3032 postimplementation. Seventy‐eight percent of transplants in the post era were for the most medically urgent (statuses 1‐3) compared to 68% for status 1A in the pre era. The median distance between the donor hospital and transplant center increased from 83 to 216 nautical miles, with an increase in total ischemic time from 3 to 3.4 hours (all P < .001). Waiting list mortality was not different across eras (14.8 vs 14.9 deaths per 100 patient‐years pre vs post respectively). Posttransplant patient survival was not different, 93.6% pre and 92.8% post. There is early evidence that the heart allocation policy has enhanced stratification of candidates by their medical urgency and broader distribution for the most medically urgent candidates with minimal impact on overall waiting list mortality and posttransplant outcomes.     

Pediatric heart transplantation at adult‐specialty centers in the United States: A multicenter registry analysis

Recent Organ Procurement and Transplantation Network bylaw revisions mandate that US transplant programs have an “approved pediatric component” in order to perform heart transplantation (HT) in patients <18 years old. The impact of this change on adolescents, a group known to be at high risk for graft loss and nonadherence, is unknown. We studied all US primary pediatric (age <18 years) HT from 2000 to 2015 to compare graft survival between centers organized mainly for adult versus pediatric care. Centers were designated as pediatric‐ or adult‐specialty care according to the ratio of pediatric:adult HT performed and minimum age of HT (pediatric‐specialty defined as ratio>0.7; adult‐specialty ratio<0.05 and minimum age >8 years). In propensity score‐matched cohorts, we observed no difference in graft loss by center type (median survival: adult 12.4 years vs pediatric 9.2 years, P = .174). Compared to the matched pediatric cohort, adult‐specialty center recipients lived closer to their transplant center (31 vs 45 miles, P = .012), and trended toward fewer out‐of‐state transplants (15 vs 25%, P = .082). Our data suggest that select adolescents can achieve similar midterm graft survival at centers organized primarily for adult HT care. Regardless of post‐HT setting, the development of care models that demonstrably improve adherence may be of greatest benefit to improving survival of this high‐risk population.     

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case‐by‐case basis for Pediatric End‐Stage Liver Disease/Mayo End‐Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009–2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2–18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26–7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53–1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99–5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.     

Simulated Regionalization of Heart and Lung Transplantation in the United States

We simulated the impact of regionalization of isolated heart and lung transplantation within United Network for Organ Sharing (UNOS) regions. Overall, 12 594 orthotopic heart transplantation (OHT) patients across 135 centers and 12 300 orthotopic lung transplantation (OLT) patients across 67 centers were included in the study. An algorithm was constructed that “closed” the lowest volume center in a region and referred its patients to the highest volume center. In the unadjusted analysis, referred patients were assigned the highest volume center's 1‐year mortality rate, and the difference in deaths per region before and after closure was computed. An adjusted analysis was performed using multivariable logistic regression using recipient and donor variables. The primary outcome was the potential number of lives saved at 1 year after transplant. In adjusted OHT analysis, 10 lives were saved (95% confidence interval [CI] 9–11) after one center closure and 240 lives were saved (95% CI 209–272) after up to five center closures per region, with the latter resulting in 1624 total patient referrals (13.2% of OHT patients). For OLT, lives saved ranged from 29 (95% CI 26–32) after one center closure per region to 240 (95% CI 224–256) after up to five regional closures, but the latter resulted in 2999 referrals (24.4% of OLT patients). Increased referral distances would severely limit access to care for rural and resource‐limited populations.     

Unintended Consequences of the New National Kidney Allocation Policy in the United States

The new national Kidney Allocation System of the Organ Procurement and Transplantation Network (OPTN), effective as of December 4, 2014, was designed to improve the chances of transplanting the most highly sensitized patients on the waitlist, those with calculated panel reactive antibody values of 98%, 99% and 100%. Recently, it was suggested that these highly sensitized patients will experience inequitable access, given the reported high prevalence of antibodies to HLA‐DP, and the fact that only about 1/3 of deceased donors are typed for HLA‐DP antigens. Here we report that 320/2948 flow cytometric crossmatches performed for the Northwestern transplant program over the past 28 months were positive solely due to HLA‐DP donor‐specific antibodies (11%; 16.5% of patients with HLA antibodies—sensitized patients). We further show that 58/207 (12%) HLA‐DR serologically matched donor‐recipient pairs had a positive B cell flow crossmatch due to donor‐specific HLA class II antibodies, and 2/34 (6%) serologic zero‐HLA‐A‐B‐DR mismatch had a positive flow crossmatch due to HLA‐DSA. We therefore provide information regarding the necessity and importance of complete donor HLA typing including both chains of the HLA‐DP antigen (encoded by HLA‐DPA1 and HLA‐DPB1) at the time of organ offer.     

First Report on the OPTN National Variance: Allocation of A2/A2B Deceased Donor Kidneys to Blood Group B Increases Minority Transplantation

In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, “variance of practice” to allow deceased donor, ABO blood group incompatible, A₂ antigen, kidney transplantation into blood group B recipients; outcomes of this cohort were compared to ABO compatible recipients. The goal of the variance was to increase the number of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti‐A IgG titers (<1:8) were eligible to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A₂/A₂B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan–Meier graft survival rates for the B recipients of A₂/A₂B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparable to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p‐value = 0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in blood group A transplants. The data support the proposition that this allocation algorithm may provide a robust mechanism to increase access of blood group B minority candidates to kidney transplantation.     

One Size Does Not Fit All—Regional Variation in the Impact of the Share 35 Liver Allocation Policy

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre–Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post–Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan–Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End‐stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ‐perfusion support at transplant post–Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre–Share 35 and post–Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post–Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting “sicker patients” with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.     

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower‐priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51‐2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39‐0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85‐0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17‐1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.     

Cytomegalovirus mismatch still negatively affects patient and graft survival in the era of routine prophylactic and preemptive therapy: A paired kidney analysis

The impact of cytomegalovirus (CMV) serostatus on kidney transplant outcomes in an era when CMV prophylactic and preemptive strategies are used routinely is not clearly established. Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, recipients with first deceased donor kidney transplant (≥18 years, 2010‐2015) were stratified into 4 groups in the main cohort: CMV‐seronegative donor (D?)/CMV‐seronegative recipient (R?), CMV‐seropositive donor (D+)/R?, D+/CMV‐seropositive recipient (R+), and D?/R+. In a paired kidney cohort, we identified 2899 pairs of D? kidney transplant with discordance of recipient serostatus (D?/R? vs D?/R+) and 4567 pairs of D+ kidney transplant with discordance of recipient serostatus (D+/R? vs D+/R+). In the main cohort, D+/R? was associated with a higher risk of graft failure (hazard ratio [HR] = 1.17, P = .01), all‐cause mortality (HR = 1.18, P < .001), and infection‐related mortality (HR = 1.38, P = .03) compared with D?/R?. In the paired kidney analysis, D+/R? was an independent risk factor for all‐cause mortality (HR = 1.21, P = .003) and infection‐related mortality (HR = 1.47, P = .04) compared with D+/R+. No difference in graft loss between D+/R? and D+/R+. CMV mismatch is still an independent risk factor for graft loss and patient mortality. The negative impact of D+/R? serostatus on mortality persists after fully matching for donor factors.     

Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non‐Renal Solid Organ Transplant

Children who receive a non‐renal solid organ transplant may develop secondary renal failure requiring kidney transplantation. We investigated outcomes of 165 pediatric kidney transplant recipients who previously received a heart, lung, or liver transplant using data from 1988 to 2012 reported to the United Network for Organ Sharing. Patient and allograft survival were compared with 330 matched primary kidney transplant (PKT) recipients. Kidney transplantation after solid organ transplant (KASOT) recipients experienced similar allograft survival: 5‐ and 10‐year graft survival was 78% and 60% in KASOT recipients, compared to 80% and 61% in PKT recipients (p = 0.69). However, KASOT recipients demonstrated worse 10‐year patient survival (75% KASOT vs. 97% PKT, p < 0.001). Competing risks analysis indicated that KASOT recipients more often experienced graft loss due to patient death (p < 0.001), whereas allograft failure per se was more common in PKT recipients (p = 0.01). To study more recent outcomes, kidney transplants performed from 2006 to 2012 were separately investigated. Since 2006, KASOT and PKT recipients had similar 5‐year graft survival (82% KASOT vs. 83% PKT, p = 0.48), although 5‐year patient survival of KASOT recipients remained inferior (90% KASOT vs. 98% PKT, p < 0.001). We conclude that despite decreased patient survival, kidney allograft outcomes in pediatric KASOT recipients are comparable to those of PKT recipients.     

The Collaborative Innovation and Improvement Network (COIIN): Effect on donor yield,waitlist mortality,transplant rates,and offer acceptance

The Organ Procurement and Transplantation Network implemented the Collaborative Improvement and Innovation Network (COIIN) to improve the use of donors with kidney donor profile index >50%. COIIN recruited 2 separate cohorts of kidney transplant programs. Cohort A included 19 programs of 44 applicants (January 1, 2017, to September 30, 2017), and cohort B included 39 programs of 47 applicants (October 1, 2017, to June 30, 2018). We investigated the effect of COIIN on kidney yield (number of kidneys transplanted from donors from whom any organ was recovered), offer acceptance, deceased donor transplant rates, and waitlist mortality rates for January 1, 2016, to March 31, 2019. COIIN did not notably affect kidney yield or waitlist mortality rates. Cohort A, but not cohort B, had significantly higher deceased donor transplant and offer acceptance rates during its intervention period than programs not in COIIN (adjusted transplant rate ratio: cohort A, _1.081.17_1.27, cohort B, _0.941.01_1.08; adjusted offer acceptance ratio: cohort A, _1.081.18_1.29, cohort B, _0.931.00_1.08). Thus, COIIN improved the use of kidneys at programs in cohort A but not at those in cohort B. Further research is necessary to understand the different effects for cohorts A and B, and further monitoring of posttransplant outcomes is required.     

New Insights Into the Alleged Kidney Donor Profile Index Labeling Effect on Kidney Utilization

The Kidney Donor Profile Index (KDPI) became a driving factor in deceased donor kidney allocation on December 4, 2014, with the implementation of the kidney allocation system (KAS). On April 20, 2016, the annual recalibration of the Kidney Donor Risk Index into KDPI was incorrectly programmed in DonorNet, resulting in erroneously high KDPI values, by between 1 and 21 percentage points (e.g. actual KDPI of 70% was displayed as 86%). The error was corrected on May 19, 2016, <24 h after being recognized. During this 30‐day period, the distribution of recipients largely resembled pre‐KAS patterns. The observed discard rate of 22.9% was higher than the post‐KAS average of 19.6% (odds ratio [OR]: 1.22) but far lower than the projected rate of 31.4% (OR: 1.96) based on the usual discard rate by KDPI relationship, suggesting clinicians and patients did not rely heavily on this single number (KDPI) in kidney‐utilization decisions. Still, risk‐adjusted analyses suggest the elevated discard rate was most likely attributable to the erroneously high KDPIs, not a shift in donor characteristics or random chance. The rise in discard rate was sharply higher for kidneys with inflated KDPI that crossed the 85% policy threshold (OR: 1.46; p = 0.049) versus those that did not (OR: 1.06; p = 0.631).     

Predictors of low risk for dropout from the liver transplant waiting list for hepatocellular carcinoma in long wait time regions: Implications for organ allocation

All patients with hepatocellular carcinoma meeting United Network for Organ Sharing T2 criteria currently receive the same listing priority for liver transplant (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the United Network for Organ Sharing database 2052 patients with T2 hepatocellular carcinoma receiving priority listing from 2011 to 2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18.3% at 1 year and 27% at 2 years. In multivariate analysis, factors associated with a lower risk of waitlist dropout included Model for End‐Stage Liver Disease‐Na < 15, Child's class A, single 2‐ to 3‐cm lesion, and α‐fetoprotein ≤20 ng/mL. The subgroup of 245 (11.9%) patients meeting these 4 criteria at LT listing had a 1‐year probability of dropout of 5.5% vs 20% for all others (P < .001). On explant, the low dropout risk group was more likely to have complete tumor necrosis (35.5% vs 24.9%, P = .01) and less likely to exceed Milan criteria (9.9% vs 17.7%, P = .03). We identified a subgroup with a low risk of waitlist dropout who should not receive the same LT listing priority.     

ABO‐Nonidentical Liver Transplantation in the United States

Under the United Network for Organ Sharing (UNOS) policy, deceased donor livers may be offered to ABO‐nonidentical candidates at each given Model for End‐Stage Liver Disease (MELD) score and to blood type B candidates at MELD ≥30. To evaluate ABO‐nonidentical liver transplantation (LT) in the United States, we examined all adult LT non–status 1 candidates, recipients and deceased liver donors from 2013 to 2015. There were 34 920 LT candidates (47% type O, 38% type A, 12% type B, 3% type AB) and 10 479 deceased liver donors (47% type O, 38% type A, 12% type B, 3% type AB). ABO‐nonidentical LT occurred in 2%, 3%, 20% and 36% of types O, A, B and AB recipients, respectively, which led to a net liver loss of 6% for type O and 2% for type A recipients but a net liver gain of 14% for type B and 55% for type AB recipients. The LT MELD scores of ABO‐identical versus ‐nonidentical recipients were 29 versus 34 for type O, 29 versus 19 for type A, 25 versus 38 for type B, and 22 versus 28 for type AB (p < 0.01). ABO‐nonidentical LT increased liver supply for candidates with blood types B and AB but decreased supply for type O and A candidates. We urge refinement of UNOS policy surrounding ABO‐nonidentical LT.