Faculty Bibliography

BACKGROUND:Recent changes in deceased donor organ allocation for livers (Share-35) and kidneys (kidney allocation system) have resulted in broader sharing of organs and increased cold ischemia time (CIT). Broader organ sharing however is not the only cause of increased CIT. METHODS:This was a retrospective registry study of CIT in same-hospital liver transplants (SHLT, n = 4347) and same-hospital kidney transplants (SHKT, n = 9707) between 2004 and 2014. RESULTS:In SHLT, median (interquartile range) CIT was 5.0 (3.5-6.5) hours versus 6.6 (5.1-8.4) hours in other-hospital LT. donation after circulatory death donors, donor biopsy, male recipient, recipient obesity, and previous transplant were associated with increased CIT. Model for End-Stage Liver Disease at transplant of 29+ or status 1a was associated with decreased CIT. SHLT CIT varied by Organ Procurement Organization and transplant-center (P < 0.01), with center median CIT ranging from 2.0 to 7.8 hours across 118 centers. In SHKT, CIT was 13.0 (8.5-19.0) hours versus 16.5 (11.3-22.6) hours in other-hospital KT. Overweight donors, donation after cardiac death donors, right-kidney, donor biopsy, recipient obesity, use of mechanical perfusion, additional KT procedures on the same day, and transplant center annual volume were associated with increased CIT. Older donor age, extended criteria donors, and underweight recipients were associated with decreased CIT. SHKT CIT varied by Organ Procurement Organization and transplant-center (P < 0.001), with center median CIT ranging from 3.3 to 29 hours across 206 centers. Transplant centers with longer SHKT also had longer SHLT (P = 0.01). CONCLUSIONS:Same-hospital transplants already have a significant amount of CIT, even without transporting the organ to another hospital.

The impact of pre-donation obesity on long-term outcomes of living kidney donors remains controversial. Published guidelines offer varying recommendations regarding BMI (kg/m² ) thresholds for donor acceptance. We examined temporal and center-level variation in BMI of accepted donors across US transplant centers. Using national transplant registry data, we performed multivariate hierarchical logistic regression modeling using pairwise comparisons (overweight, BMI: 25-29.9; mildly obese, BMI: 30-34.9; very obese, BMI: ≥35; versus normal BMI: 18.5-24.9). Metrics of heterogeneity, including median odds ratio (MOR), were calculated. Among 90 013 living kidney donors, 2001-2016, proportions who were very obese decreased and proportions who were mildly obese or overweight increased. Significant center-level heterogeneity was noted in BMI of accepted donors; the MOR varied from 1.10 for overweight to 1.93 for very obese donors. At centers located in the 10 states with the highest general population obesity rates, adjusted odds of very obese donor status were 185% higher (reference: normal BMI) than in states with the lowest obesity rates. Although there is a declining trend in acceptance of very obese living kidney donors, variation across centers is significant. Furthermore, local population obesity rates may affect the decision to accept obese individuals as donors.

To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.

OBJECTIVE:African Americans and other minorities are known to face barriers to health care influencing their access to organ transplantation but it is not known whether these barriers exist among pediatric liver transplant waitlist candidates. We sought to determine whether outcomes on the waitlist (ie, mortality, deceased donor liver transplantation [DDLT], and living-donor liver transplantation [LDLT]) varied by race/ethnicity. METHODS:National registry data were studied to estimate the race/ethnicity-specific risk of waitlist mortality, DDLT and LDLT in children (<18 years) waitlisted between March 2002 and March 2015. RESULTS:There was no evidence of racial/ethnic disparities in waitlist mortality. Compared to Caucasians, LDLT varied by race/ethnicity, with only 6.7% African Americans and 10.3% Hispanic children receiving LDLT compared with 12.4% Caucasian, 13.3% Asian, and 9.4% mix/other children. In an adjusted Cox proportional hazards model, African Americans were half as likely as Caucasians to use LDLT (hazard ratio [HR]: 0.410.550.73) but had similar use of DDLT (HR: 0.981.061.16). In a model that considered mortality, DDLT, and LDLT as competing risks, African Americans had significantly reduced incidence of LDLT (subhazard ratio [sHR]: 0.410.560.75) compared to Caucasians, but increased use of DDLT (sHR: 1.061.161.26). CONCLUSIONS:Compared to Caucasian children, African-American children are less likely to use LDLT but have higher rates of DDLT and similar survival on the waitlist. Additional research is necessary to understand the clinical and socioeconomic factors contributing to lower utilization of LDLT among African-American children awaiting transplantation.

The perception of living kidney donation-related financial burden affects willingness to donate and the experience of donation, yet no existing tools identify donors who are at higher risk of perceived financial burden. We sought to identify characteristics that predicted higher risk of perceived financial burden. We surveyed 51 living kidney donors (LKDs) who donated from 01/2015 to 3/2016 about socioeconomic characteristics, predonation cost concerns, and perceived financial burden. We tested associations between both self-reported and ZIP code-level characteristics and perceived burden using Fisher's exact test and bivariate modified Poisson regression. Donors who perceived donation-related financial burden were less likely to have an income above their ZIP code median (14% vs. 72%, P = .006); however, they were more likely than donors who did not perceive burden to rent their home (57% vs. 16%, P = .03), have an income <$60 000 (86% vs. 20%, P = .002), or have had predonation cost concerns (43% vs. 7%, P = .03). Perceived financial burden was 3.6-fold as likely among those with predonation cost concerns and 10.6-fold as likely for those with incomes <$60 000. Collecting socioeconomic characteristics and asking about donation-related cost concerns prior to donation might allow transplant centers to target financial support interventions toward potential donors at higher risk of perceiving donation-related financial burden.

BACKGROUND:The Organ Procurement and Transplantation Network has implemented medical criteria to determine which candidates are most appropriate for simultaneous liver-kidney (SLK) transplantation in comparison to liver-alone transplantation. We investigated prepolicy center-level variation among SLK listing practice, in light of such criteria. METHODS:We identified 4736 SLK-eligible candidates after Share-35 in the United States. We calculated the proportion of candidates at each center who were listed for SLK transplantation within 6 months of eligibility. Multilevel logistic regression and parametric survival model was used to estimate the center-specific probability of SLK listing, adjusting for patient and center-level characteristics. RESULTS:Among 4736 SLK-eligible candidates, 64.8% were listed for SLK within 6 months of eligibility. However, the percentage of SLK listing ranged from 0% to 100% across centers. African American race, male sex, transplant history, diabetes, and hypertension were associated with a higher likelihood of SLK listing. Conversely, older age was associated with a lower likelihood of SLK listing. After adjusting for candidate characteristics, the percentage of SLK listing still ranged from 3.8% to 80.2% across centers; this wide variation persisted even after further adjusting for center-level characteristics. CONCLUSIONS:There was significant prepolicy center-level variation in SLK listing for SLK-eligible candidates. Implementation of standardized SLK listing practices may reduce center-level variation and equalize access for SLK candidates across the United States.

Transplant candidates who accept a kidney labeled increased risk for disease transmission (IRD) accept a low risk of window period infection, yet those who decline must wait for another offer that might harbor other risks or never even come. To characterize survival benefit of accepting IRD kidneys, we used 2010-2014 Scientific Registry of Transplant Recipients data to identify 104 998 adult transplant candidates who were offered IRD kidneys that were eventually accepted by someone; the median (interquartile range) Kidney Donor Profile Index (KDPI) of these kidneys was 30 (16-49). We followed patients from the offer decision until death or end-of-study. After 5 years, only 31.0% of candidates who declined IRDs later received non-IRD deceased donor kidney transplants; the median KDPI of these non-IRD kidneys was 52, compared to 21 of the IRDs they had declined. After a brief risk period in the first 30 days following IRD acceptance (adjusted hazard ratio [aHR] accept vs decline: _1.22 2.06_3.49 , P = .008) (absolute mortality 0.8% vs. 0.4%), those who accepted IRDs were at 33% lower risk of death 1-6 months postdecision (aHR _0.50 0.67_0.90 , P = .006), and at 48% lower risk of death beyond 6 months postdecision (aHR _0.46 0.52_0.58 , P < .001). Accepting an IRD kidney was associated with substantial long-term survival benefit; providers should consider this benefit when counseling patients on IRD offer acceptance.

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25-23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02-1.09, P < .01). However, there was not a significant association between CIT and all-cause graft failure (adjusted hazard ratio [aHR]: 1.01, 95% CI: 0.98-1.04, P = .4), death-censored graft failure ( [aHR]: 1.02, 95% CI, 0.98-1.06, P = .4), or mortality (aHR 1.00, 95% CI, 0.96-1.04, P > .9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.

BACKGROUND:HIV-infected (HIV+) donor organs can be transplanted into HIV+ recipients under the HIV Organ Policy Equity (HOPE) Act. Quantifying HIV+ donor referrals received by organ procurement organizations (OPOs) is critical for HOPE Act implementation. METHODS:We surveyed the 58 USA OPOs regarding HIV+ referral records and newly discovered HIV+ donors. Using data from OPOs that provided exact records and CDC HIV prevalence data, we projected a national estimate of HIV+ referrals. RESULTS:Fifty-five (95%) OPOs reported HIV+ referrals ranging from 0 to 276 and newly discovered HIV+ cases ranging from 0 to 10 annually. Six OPOs in areas of high HIV prevalence reported more than 100 HIV+ donor referrals. Twenty-seven (47%) OPOs provided exact HIV+ referral records and 28 (51%) OPOs provided exact records of discovered HIV+ cases, totaling 1450 HIV+ referrals and 39 discovered HIV+ donors in the prior year. These OPOs represented 67% and 59% of prevalent HIV cases in the USA; thus, we estimated 2164 HIV+ referrals and 66 discovered HIV+ cases nationally per year. CONCLUSIONS:OPOs reported a high volume of HIV+ referrals annually, of which a subset will be medically eligible for donation. Particularly in areas of high HIV prevalence, OPOs require ongoing support to implement the HOPE Act.

The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was _1.75 1.81_1.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR = _1.35 1.40_1.45 , P < .01) and a three-year dialysis vintage was associated with a 1.57-fold increase (IRR = _1.56 1.57_1.59 , P < .001) in transplant rate. For pediatric candidates, MIRR was even more pronounced, at _1.66 1.92_2.27 . There was no change in geographic disparities with KAS (P = .3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT.