Faculty Bibliography

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.

PURPOSE OF REVIEW:The HIV Organ Policy Equity (HOPE) Act, signed in 2013, reversed the federal ban on HIV-to-HIV transplantation. In this review, we examine the progress in HOPE implementation, the current status of HIV-to-HIV transplantation, and remaining challenges. RECENT FINDINGS:Pursuant to the HOPE Act, the Department of Health and Human Services revised federal regulations to allow HIV-to-HIV transplants under research protocols adherent to criteria published by the National Institutes of Health. The first HIV-to-HIV kidney and liver transplants were performed at Johns Hopkins in March of 2016. Legal and practical challenges remain. Further efforts are needed to educate potential HIV+ donors and to support Organ Procurement Organizations. As of November 2017, there are 22 transplant centers approved to perform HIV-to-HIV transplants in 10 United Network for Organ Sharing regions. To date, 16 Organ Procurement Organizations in 22 states have evaluated HIV+ donors. The National Institutes of Health-funded HOPE in Action: A Multicenter Clinical Trial of HIV-to-HIV Deceased Donor (HIVDD) Kidney Transplantation Kidney Trial will launch at 19 transplant centers in December of 2017. A HOPE in Action Multicenter HIVDD Liver Trial is in development. SUMMARY:Significant progress toward full HOPE implementation has been made though barriers remain. Some challenges are unique to HIV-HIV transplantation, whereas others are amplifications of issues across the current transplant system. In addition to a public health benefit for all transplant candidates in the United States, partnership on the HOPE Act has the potential to address systemic challenges to national donation and transplantation.

30% of kidney transplant recipients are readmitted in the first month post-transplant. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95%CI: 1.13-1.46; P<0.001). Risk peaked at 6-12 months (RR 1.67; 95%CI: 1.49-1.87; P<0.001), attenuating by 24-36 months (RR 1.24; 95%CI: 1.10-1.40; P<0.001). ILDKTs had a 5.86-fold higher readmission risk (95%CI: 4.96-6.92; P<0.001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85; 95%CI: 0.77-0.95; P=0.002) and 24-36 months (RR 0.74; 95% CI: 0.66-0.84; P<0.001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.

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.

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.

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:Frailty has been recognized as an important medical syndrome in older adults. Growing literature supports the clinical application of frailty but US older adults' perceptions of frailty have not been explored. We aim to examine perceptions and informational needs about frailty among older adults. METHODS:This was a qualitative study involving focus groups of community-dwelling older adults with diverse age and frailty status. We explored participants' beliefs and knowledge about frailty and informational needs about frailty as a medical syndrome. RESULTS:The participants' mean age was 76.3. Of the 29 participants, 21 (72%) were female, and 21 (72%) were white. We identified three major themes: 1) Older adults' perceptions of frailty differed from the definition used in medical literature; they often perceived a psychological component to being frailty and some were skeptical of the syndromic definition based on multiple symptoms. 2) Compared to participants who were non-frail or pre-frail, participants who were frail were more receptive to discussing their frailty status with clinicians; 3) Participants wanted know about how to treat or prevent frailty and the risks associated with being frail. Many participants felt that these information can be conveyed without necessarily using the specific term "frail", which they perceived to have a negative connotation. CONCLUSIONS:Older adults, especially those who are frail, may be interested to discuss frailty as a medical syndrome. However, negative perceptions are associated with the term "frail" and may be a barrier to clinical application of frailty. Further research is needed to understand acceptable ways for communicating about frailty in clinical practice.