Faculty Bibliography

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.

Many deceased-donor and living-donor kidney transplants (KTs) rely on commercial airlines for transport. However, the coronavirus-19 pandemic has drastically impacted the commercial airline industry. To understand potential pandemic-related disruptions in the transportation network of kidneys across the United States, we used national flight data to compare scheduled flights during the pandemic vs 1-year earlier, focusing on Organ Procurement Organization (OPO) pairs between which kidneys historically most likely traveled by direct flight (High Volume by direct Air transport OPO Pairs, HVA-OPs). Across the United States, there were 39% fewer flights in April 2020 vs April 2019. Specific to the kidney transportation network, there were 65.1% fewer flights between HVA-OPs, with considerable OPO-level variation (interquartile range [IQR] 54.7%-75.3%; range 0%-100%). This translated to a drop in median number of flights between HVA-OPs from 112 flights/wk in April 2019 to 34 in April 2020 (P < .001), and a rise in wait time between scheduled flights from 1.5 hours in April 2019 (IQR 0.76-3.3) to 4.9 hours in April 2020 (IQR 2.6-11.2; P < .001). Fewer flights and longer wait times can impact logistics as well as cold ischemia time; our findings motivate an exploration of creative approaches to KT transport as the impact of this pandemic on the airline industry evolves.

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.

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:Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS:Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS:Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS:The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

BACKGROUND:Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer. METHODS:We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted). RESULTS:Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03). CONCLUSIONS:Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

In March 2020, coronavirus disease 2019 (COVID-19) spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center levels, accounting statistically for waitlist composition. Using Scientific Registry of Transplant Recipients data, we compared data on observed waitlist registrations, waitlist mortality, and living-donor and deceased-donor kidney transplants (LDKT/DDKT) March 15-April 30, 2020 to expected events calculated from preepidemic data January 2016-February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all P < .001). Only 12 centers performed LDKT March 15-31; by April 30, 40 centers had resumed LDKT. The decline in new listings and DDKT was greater among states with higher per capita confirmed COVID-19 cases. The number of waitlist deaths was 2.2-fold higher than expected in the 5 states with highest COVID-19 burden (P < .001). DCD DDKT and regional/national imports declined nationwide but most steeply in states with the highest COVID-19 burden. The COVID-19 epidemic has resulted in substantial changes to KT; we must adapt and learn rapidly to continue to provide safe access to transplantation and limit the growing indirect toll of an already deadly disease.

The first sustained increase in live kidney donation in the United States in 15 years was observed from 2017 to 2019. To help sustain this surge, we studied 35 900 donors (70.3% white, 14.5% Hispanic, 9.3% black, 4.4% Asian) to understand the increase in 2017-2019 vs 2014-2016 using Poisson regression. Among biologically related donors aged <35, 35-49, and ≥50 years, the number of donors did not change across race/ethnicity but increased by 38% and 29% for Hispanic and black ≥50. Among unrelated donors <35, 35-49, and ≥50, white donors increased by 18%, 14%, and 27%; Hispanic donors <35 did not change but increased by 22% and 35% for 35-49 and ≥50; black donors <35 declined by 23% and did not change for 35-49 and ≥50; Asian donors did not change. Among kidney paired donors <35, 35-49, and ≥50, white donors increased by 42%, 50%, and 68%; Hispanic donors <35 and 35-49 increased by 36% and 55% and did not change for ≥50; black donors did not change; Asian donors <35 did not change but increased by 107% and 82% for 35-49 and ≥50. The increase in donation was driven predominantly by unrelated and paired white donors. Donation among unrelated black individuals should be promoted.

Clinical decision-making in kidney transplant (KT) during the coronavirus disease 2019 (COVID-19) pandemic is understandably a conundrum: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. To quantify the benefit/harm of KT in this context, we conducted a simulation study of immediate-KT vs delay-until-after-pandemic for different patient phenotypes under a variety of potential COVID-19 scenarios. A calculator was implemented (http://www.transplantmodels.com/covid_sim), and machine learning approaches were used to evaluate the important aspects of our modeling. Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority when modeling deceased donor KT) had greatest influence on benefit/harm. In most scenarios of COVID-19 dynamics and patient characteristics, immediate KT provided survival benefit; KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (eg, ≥50% fatality) than for waitlist registrants. Our simulations suggest that KT could be beneficial in many centers if local resources allow, and our calculator can help identify patients who would benefit most. Furthermore, as the pandemic evolves, our calculator can update these predictions.

The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N = 98 620), and associations (adjusted hazard ratio, _LCL aHR_UCL ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, _1.08 1.22_1.38 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5 years (aHR: short-acting _1.29 1.39_1.48 ; long-acting _1.12 1.25_1.40 ; both _1.46 1.74_2.07 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.