Faculty Bibliography

Importance:Over the past 2 decades, there has been increased attention and effort to reduce disparities in live donor kidney transplantation (LDKT) for black, Hispanic, and Asian patients with end-stage kidney disease. The goal of this study was to investigate whether these efforts have been successful. Objective:To estimate changes over time in racial/ethnic disparities in LDKT in the United States, accounting for differences in death and deceased donor kidney transplantation. Design, Setting, and Participants:A secondary analysis of a prospectively maintained cohort study conducted in the United States of 453 162 adult first-time kidney transplantation candidates included in the Scientific Registry of Transplant Recipients between January 1, 1995, and December 31, 2014, with follow-up through December 31, 2016. Exposures:Race/ethnicity. Main Outcomes and Measures:The primary study outcome was time to LDKT. Multivariable Cox proportional hazards and competing risk models were constructed to assess changes in racial/ethnic disparities in LDKT among adults on the deceased donor kidney transplantation waiting list and interaction terms were used to test the statistical significance of temporal changes in racial/ethnic differences in receipt of LDKT. The adjusted subhazard ratios are estimates derived from the multivariable competing risk models. Data were categorized into 5-year increments (1995-1999, 2000-2004, 2005-2009, 2010-2014) to allow for an adequate sample size in each analytical cell. Results:Among 453 162 adult kidney transplantation candidates (mean [SD] age, 50.9 [13.1] years; 39% were women; 48% were white; 30%, black; 16%, Hispanic; and 6%, Asian), 59 516 (13.1%) received LDKT. Overall, there were 39 509 LDKTs among white patients, 8926 among black patients, 8357 among Hispanic patients, and 2724 among Asian patients. In 1995, the cumulative incidence of LDKT at 2 years after appearing on the waiting list was 7.0% among white patients, 3.4% among black patients, 6.8% among Hispanic patients, and 5.1% among Asian patients. In 2014, the cumulative incidence of LDKT was 11.4% among white patients, 2.9% among black patients, 5.9% among Hispanic patients, and 5.6% among Asian patients. From 1995-1999 to 2010-2014, racial/ethnic disparities in the receipt of LDKT increased (P < .001 for all statistical interaction terms in adjusted models comparing white patients vs black, Hispanic, and Asian patients). In 1995-1999, compared with receipt of LDKT among white patients, the adjusted subhazard ratio was 0.45 (95% CI, 0.42-0.48) among black patients, 0.83 (95% CI, 0.77-0.88) among Hispanic patients, and 0.56 (95% CI, 0.50-0.63) among Asian patients. In 2010-2014, compared with receipt of LDKT among white patients, the adjusted subhazard ratio was 0.27 (95% CI, 0.26-0.28) among black patients, 0.52 (95% CI, 0.50-0.54) among Hispanic patients, and 0.42 (95% CI, 0.39-0.45) among Asian patients. Conclusions and Relevance:Among adult first-time kidney transplantation candidates in the United States who were added to the deceased donor kidney transplantation waiting list between 1995 and 2014, disparities in the receipt of live donor kidney transplantation increased from 1995-1999 to 2010-2014. These findings suggest that national strategies for addressing disparities in receipt of live donor kidney transplantation should be revisited.

OBJECTIVE:To evaluate changes in patient and graft survival for pediatric liver transplant recipients since 2002, and to determine if these outcomes vary by graft type (whole liver transplant, split liver transplant [SLT], and living donor liver transplant [LDLT]). STUDY DESIGN:We evaluated patient and graft survival among pediatric liver-only transplant recipients the PELD/MELD system was implemented using the Scientific Registry of Transplant Recipients. RESULTS:). CONCLUSIONS:In recent years, outcomes after the use of technical variant grafts are comparable with whole grafts, and may be superior for LDLT. Greater use of technical variant grafts might provide an opportunity to increase organ supply without compromising post-transplant outcomes.

Currently, there is debate among the liver transplant community regarding the most appropriate mechanism for organ allocation: urgency-based (MELD) versus utility-based (survival benefit). We hypothesize that MELD and survival benefit are closely associated, and therefore, our current MELD-based allocation already reflects utility-based allocation. We used generalized gamma parametric models to quantify survival benefit of LT across MELD categories among 74 196 adult liver-only active candidates between 2006 and 2016 in the United States. We calculated time ratios (TR) of relative life expectancy with transplantation versus without and calculated expected life years gained after LT. LT extended life expectancy (TR > 1) for patients with MELD > 10. The highest MELD was associated with the longest relative life expectancy (TR = _1.05 1.20_1.37 for MELD 11-15, _2.29 2.49_2.70 for MELD 16-20, _5.30 5.72_6.16 for MELD 21-25, _15.12 16.35_17.67 for MELD 26-30; _39.26 43.21_47.55 for MELD 31-34; _120.04 128.25_137.02 for MELD 35-40). As a result, candidates with the highest MELD gained the most life years after LT: 0.2, 1.5, 3.5, 5.8, 6.9, 7.2 years for MELD 11-15, 16-20, 21-25, 26-30, 31-34, 35-40, respectively. Therefore, prioritizing candidates by MELD remains a simple, effective strategy for prioritizing candidates with a higher transplant survival benefit over those with lower survival benefit.

BACKGROUND:The Fried frailty phenotype, a measure of physiologic reserve defined by 5 components (exhaustion, unintentional weight loss, low physical activity, slow walking speed, and poor grip strength), is associated with poor outcomes among ESRD patients. However, these 5 components may not fully capture physiologic reserve in this population. We aimed to ascertain opinions of ESRD clinicians and patients about the usefulness of the Fried frailty phenotype and interventions to improve frailty in ESRD patients, and to identify novel components to further characterize frailty in ESRD. METHODS:Clinicians who treat adults with ESRD completed a 2-round Delphi study (n = 41 and n = 36, respectively; response rate = 87%). ESRD patients completed a survey at transplant evaluation (n = 460; response rate = 81%). We compared clinician and patient opinions on the constituent components of frailty. RESULTS:Clinicians were more likely than patients to say that ESRD makes patients frail (97.6% vs. 60.2%). There was consensus among clinicians that exhaustion, low physical activity, slow walking speed, and poor grip strength characterize frailty in ESRD patients; however, 29% of clinicians thought weight loss was not relevant. Patients were less likely than clinicians to say that the 5 Fried frailty components were relevant. Clinicians identified 10 new ESRD-specific potential components including falls (64%), physical decline (61%), and cognitive impairment (39%). Clinicians (83%) and patients (80%) agreed that intradialytic foot-peddlers might make ESRD patients less frail. CONCLUSIONS:There was consensus among clinicians and moderate consensus among patients that frailty is more common in ESRD. Weight loss was not seen as relevant, but new components were identified. These findings are first steps in refining the frailty phenotype and identifying interventions to improve physiologic reserve specific to ESRD patients.

The Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time-to-event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014), Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, P = .17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, P < .001; Era 3 aHR: 0.33, 95% CI: 0.21-0.53, P < .001) whereas the youngest registrants aged 0-6 experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR: 0.79, 95% CI: 0.64-0.98, P = .03). Thus, while overall DDKT likelihood remained stable with the introduction of KAS, registrants ≤ 6 years of age were disadvantaged, warranting further study to ensure equitable access to transplantation.

Introduction:Cognitive decline is common and increases mortality risk in hemodialysis patients. Intradialytic interventions like cognitive training (CT) and exercise training (ET) may preserve cognitive function. Methods:values were generated from linear regression. Results: = 0.16) for ET. Conclusion:Preliminary findings of our pilot study suggested that cognitive decline in psychomotor speed and executive function is possibly prevented by intradialytic CT and ET. These preliminary pilot findings should be replicated.

Frailty is prevalent in liver transplant candidates, but little is known of what happens to frailty after liver transplantation. We analyzed data for 214 adult liver transplant recipients who had ≥1 frailty assessment using the Liver Frailty Index (LFI) at 3- (n = 178), 6- (n = 139), or 12- (n = 107) months posttransplant (higher values=more frail). "Frail" and "robust" were defined as LFI ≥4.5 and <3.2. Median pre-liver transplant LFI was 3.7, and was worse at 3 months (3.9; P = .02), similar at 6 months (3.7; P = .07), and improved at 12 months (3.4; P < .001). The percentage who were robust pre- and 3-, 6-, and 12-months posttransplant were 25%, 14%, 28%, and 37%; the percentage frail were 21%, 21%, 10%, and 7%. In univariable analysis, each 0.1 pretransplant LFI point more frail was associated with a decreased odds of being robust at 3- (odds ratio [OR] 0.75), 6- (OR 0.77), and 12-months (OR 0.90) posttransplant (P ≤ .001), which did not change substantially with multivariable adjustment. In conclusion, frailty worsens 3 months posttransplant and improves modestly by 12 months, but fewer than 2 of 5 patients achieve robustness. Pretransplant LFI was a potent predictor of posttransplant robustness. Aggressive interventions aimed at preventing frailty pretransplant are urgently needed to maximize physical health after liver transplantation.

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.

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.