Faculty Bibliography

BACKGROUND:There is concern in the transplant community that outcomes for the most highly sensitized recipients might be poor under Kidney Allocation System (KAS) high prioritization. METHODS:To study this, we compared posttransplant outcomes of 525 pre-KAS (December 4, 2009, to December 3, 2014) calculated panel-reactive antibodies (cPRA)-100% recipients to 3026 post-KAS (December 4, 2014, to December 3, 2017) cPRA-100% recipients using SRTR data. We compared mortality and death-censored graft survival using Cox regression, acute rejection, and delayed graft function (DGF) using logistic regression, and length of stay (LOS) using negative binomial regression. RESULTS:Compared with pre-KAS recipients, post-KAS recipients were allocated kidneys with lower Kidney Donor Profile Index (median 30% versus 35%, P < 0.001) but longer cold ischemic time (CIT) (median 21.0 h versus 18.6 h, P < 0.001). Compared with pre-KAS cPRA-100% recipients, those post-KAS had higher 3-year patient survival (93.6% versus 91.4%, P = 0.04) and 3-year death-censored graft survival (93.7% versus 90.6%, P = 0.005). The incidence of DGF (29.3% versus 29.2%, P = 0.9), acute rejection (11.2% versus 11.7%, P = 0.8), and median LOS (5 d versus 5d, P = 0.2) were similar between pre-KAS and post-KAS recipients. After accounting for secular trends and adjusting for recipient characteristics, post-KAS recipients had no difference in mortality (adjusted hazard ratio [aHR]: 0.861.623.06, P = 0.1), death-censored graft failure (aHR: 0.521.001.91, P > 0.9), DGF (adjusted odds ratio [aOR]: 0.580.861.27, P = 0.4), acute rejection (aOR: 0.610.941.43, P = 0.8), and LOS (adjusted LOS ratio: 0.981.161.36, P = 0.08). CONCLUSIONS:We did not find any statistically significant worsening of outcomes for cPRA-100% recipients under KAS, although longer-term monitoring of posttransplant mortality is warranted.

RATIONALE & OBJECTIVE:Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. PREDICTORS:Cognitive impairment (3MS score<80). OUTCOMES:Listing, waitlist mortality, and kidney transplantation. ANALYTICAL APPROACH:We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. RESULTS:=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. LIMITATIONS:Single measure of cognitive impairment. CONCLUSIONS:Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.

Background/UNASSIGNED:The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions. To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality. Methods/UNASSIGNED:To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020. Results/UNASSIGNED:We found low rates of COVID-19 among donors and HCWs (0%-1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%-20%), and considerable mortality (7%-13%) among those who tested positive. Conclusions/UNASSIGNED:These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic.

COVID-19 is a novel, rapidly changing pandemic: consequently, evidence-based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center-level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID-19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID-19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID-19. Shortage of COVID-19 tests was reported by 42.5%. Respondents reported a total of 148 COVID-19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center-level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence-based practices.

Background/UNASSIGNED:Caring for dialysis patients is difficult, and this burden often falls on a spouse or cohabiting partner (henceforth referred to as caregiver-partners). At the same time, these caregiver-partners often come forward as potential living kidney donors for their loved ones who are on dialysis (henceforth referred to as patient-partners). Caregiver-partners may experience tangible benefits to their well-being when their patient-partner undergoes transplantation, yet this is seldom formally considered when evaluating caregiver-partners as potential donors. Methods/UNASSIGNED:To quantify these potential benefits, we surveyed caregiver-partners of dialysis patients and kidney transplant (KT) recipients (N = 99) at KT evaluation or post-KT. Using validated tools, we assessed relationship satisfaction and caregiver burden before or after their patient-partner's dialysis initiation and before or after their patient-partner's KT. Results/UNASSIGNED: = 0.3). Conclusions/UNASSIGNED:These benefits in caregiver burden and relationship quality support special consideration for spouses and partners in risk-assessment of potential kidney donors, particularly those with risk profiles slightly exceeding center thresholds.

BACKGROUND AND OBJECTIVES:Black patients referred for kidney transplantation have surpassed many obstacles but likely face continued racial disparities before transplant. The mechanisms that underlie these disparities are unclear. We determined the contributions of socioeconomic status (SES) and comorbidities as mediators to disparities in listing and transplant. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:=1561 white) of patients with kidney failure who were referred for and started the transplant process (2009-2018). We estimated the direct and indirect effects of SES (self-reported income, education, and employment) and medical comorbidities (self-reported and chart-abstracted) as mediators of racial disparities in listing using Cox proportional hazards analysis with inverse odds ratio weighting. Among the 983 black and 1085 white candidates actively listed, we estimated the direct and indirect effects of SES and comorbidities as mediators of racial disparities on receipt of transplant using Poisson regression with inverse odds ratio weighting. RESULTS:Within the first year, 876 (60%) black and 1028 (66%) white patients were waitlisted. The relative risk of listing for black compared with white patients was 0.76 (95% confidence interval [95% CI], 0.69 to 0.83); after adjustment for SES and comorbidity, the relative risk was 0.90 (95% CI, 0.83 to 0.97). The proportion of the racial disparity in listing was explained by SES by 36% (95% CI, 26% to 57%), comorbidity by 44% (95% CI, 35% to 61%), and SES with comorbidity by 58% (95% CI, 44% to 85%). There were 409 (42%) black and 496 (45%) white listed candidates transplanted, with a median duration of follow-up of 3.9 (interquartile range, 1.2-7.1) and 2.8 (interquartile range, 0.8-6.3) years, respectively. The incidence rate ratio for black versus white candidates was 0.87 (95% CI, 0.79 to 0.96); SES and comorbidity did not explain the racial disparity. CONCLUSIONS:SES and comorbidity partially mediated racial disparities in listing but not for transplant.

BACKGROUND AND OBJECTIVES:Mortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing. RESULTS:=0.72). CONCLUSIONS:Codispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.

BACKGROUND:Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that antithymocyte globulin (ATG) might increase HCV-related complications. METHODS:Using Scientific Registry of Transplant Recipients and Medicare claims data, we studied 6780 HCV+ and 139 681 HCV- KT recipients in 1999-2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (versus IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (versus IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression. RESULTS:HCV+ recipients were less likely to receive ATG than HCV- recipients (living donor, adjusted odds ratio [aOR] = 0.640.770.91; deceased donor, aOR = 0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-y crude incidence = 11.6% versus 12.6%; aOR = 0.680.820.99). There was no significant difference in the risks of graft failure (adjusted hazard ratio [aHR] = 0.861.001.17), death (aHR = 0.850.951.07), liver transplant registration (aHR = 0.580.971.61), and cirrhosis (aHR = 0.730.921.16). CONCLUSIONS:Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.

OBJECTIVE:To determine if the association of frailty and waitlist mortality varies by candidate age. BACKGROUND:Frailty, a construct developed in geriatrics, is a state of decreased physiologic reserve, and is associated with mortality while awaiting liver transplantation (LT). However, older candidates have high comorbidity burden and less physiologic reserve, so the relationship between frailty and waitlist mortality may vary by candidate age. METHODS:We studied adults listed for LT at 2 transplant centers. The liver frailty index (grip strength, chair stands, balance) was measured at evaluation, with frailty defined as liver frailty index  ≥ 4.5. We compared the prevalence of frailty in older (≥65 yr) and younger (18-64 yr) candidates. We studied the association between frailty, age, interaction between the 2, and waitlist mortality using competing risks regression adjusted for sex, BMI, and MELDNa. RESULTS:Among 882 LT candidates, 16.6% were ≥ 65 years. Older candidates were more likely to be frail (33.3% vs 21.7%, P = 0.002). Older age [adjusted subhazard ratio (aSHR): 2.16, 95% CI: 1.51-3.09, P < 0.001] and frailty (aSHR: 1.92, 95% CI: 1.38-2.67, P < 0.001) were independently associated with higher risk of waitlist mortality. However, the association between waitlist mortality and frailty did not vary by candidate age (aSHR of frailty for younger patients: 1.90, 95% CI: 1.28-2.80, P = 0.001; aSHR of frailty for older patients: 1.98, 95% CI: 1.07-3.67, P = 0.03; P interaction = 0.9). CONCLUSIONS:Older candidates experienced higher rates of frailty than younger candidates. However, regardless of age, frailty was associated with nearly 2-fold increased risk of waitlist mortality. Our data support the applicability of the frailty concept to the whole LT population and can guide the development of prehabilitation programs targeting frailty in LT patients of all ages.

BACKGROUND:We sought to identify factors that are associated with LOS following pediatric (<18 years) liver transplantation in order to provide personalized counseling and discharge planning for recipients and their families. METHODS:We identified 2726 infants (≤24 months) and 3210 children (>24 months) who underwent pediatric liver-only transplantation from 2002-2017 using the Scientific Registry of Transplant Recipients. We used multilevel multivariable negative binomial regression to analyze associations between LOS and recipient and donor characteristics and calculated the MLOSR to quantify heterogeneity in LOS across centers. RESULTS:) were associated with a longer LOS. The MLOSR was 1.25 in infants and 1.26 in children, meaning if an infant received a transplant at another center with a longer LOS, we would expect a 1.25-fold difference in LOS driven by center practices alone. CONCLUSIONS:While center-level practices account for substantial variation in LOS, consideration of donor and recipient factors can help clinicians provide more personalized counseling for families of pediatric liver transplant candidates.