Faculty Bibliography

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007-2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0-14 days, 15-182 days, and 183-365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, _LCL aOR_UCL ). Among 23,565 donors, opioid prescriptions were highest during days 0-14 (36.6%), but 12.6% of donors filled opioids during days 183-365. NSAID prescriptions rose from 0.5% during days 0-14 to 3.3% during days 183-365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183-365 included obesity (aOR,_1.24 1.38_1.53 ), less than college education (aOR,_1.19 1.31_1.43 ), smoking (aOR,_1.33 1.45_1.58 ), and nephrectomy complications (aOR,_1.11 1.29_1.49 ). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new-onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer-term outcome implications to help inform safe analgesic regimen choices after donation.

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.

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 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.

The transmission of cancer from a donor organ is a rare event but has important consequences. Aim of this systematic review was to summarize all the published evidence on cancer transmission in kidney recipients. We reviewed published case reports and series describing the outcome of recipients with donor-transmitted cancer until August 2019. A total of 128 papers were included, representing 234 recipients. The most common transmitted cancers were lymphoma (n = 48, 20.5%), renal cancer (42, 17.9%), melanoma (40, 17.1%), non-small cell lung cancer (n = 13, 5.6%), neuroendocrine cancers comprising small cell lung cancer (n = 11, 4.7%) and choriocarcinoma (n = 10, 4.3%). There was a relative lack of glioblastoma and gastrointestinal cancers with only 6 and 5 cases, respectively. Melanoma and lung cancer had the worst prognosis, with 5-years overall survival of 43% and 19%, respectively; while renal cell cancer and lymphomas had a favorable prognosis with 5-years overall survival of 93 and 63%, respectively. Metastasis of cancer outside the graft was the most important adverse prognostic factor. Overall reporting was good, but information on donors' cause of death and investigations at procurement was often lacking. Epidemiology of transmitted cancer has evolved, thanks to screening with imaging and blood tests, as choriocarcinoma transmission have almost abolished, while melanoma and lymphoma are still difficult to detect and prevent.

Kidney transplant recipients who develop symptoms consistent with coronavirus disease 2019 (COVID-19) are bringing unique challenges to health care professionals. Telemedicine has surged dramatically since the pandemic in effort to maintain patient care and reduce the risk of COVID-19 exposure to patients, health care workers, and the public. Herein we present reports of 3 kidney transplant recipients with COVID-19 who were managed using telemedicine via synchronous video visits integrated with an electronic medical record system, from home to inpatient settings. We demonstrate how telemedicine helped assess, diagnose, triage, and treat patients with COVID-19 while avoiding a visit to an emergency department or outpatient clinic. While there is limited information about the duration of viral shedding for immunosuppressed patients, our findings underscore the importance of using telemedicine in the follow-up care for kidney transplant recipients with COVID-19 who have recovered from symptoms but might have persistently positive nucleic acid tests. Our experience emphasizes the opportunities of telemedicine in the management of kidney transplant recipients with COVID-19 and in the maintenance of uninterrupted follow-up care for such immunosuppressed patients with prolonged viral shedding. Telemedicine may help increase access to care for kidney transplant recipients during and beyond the pandemic as it offers a prompt, safe, and convenient platform in the delivery of care for these patients. Yet, to advance the practice of telemedicine in the field of kidney transplantation, barriers to increasing the widespread implementation of telemedicine should be removed, and research studies are needed to assess the effectiveness of telemedicine in the care of kidney transplant recipients.

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 light of changes in donor/recipient case-mix and increased cold ischemia times under the Kidney Allocation System (KAS), there is some concern that cPRA 100% recipients might be doing poorly under KAS. We used granular, single-center data on 109 cPRA 100% deceased donor kidney transplant (DDKT) recipients to study post-KAS posttransplant outcomes not readily available in national registry data. We found that 3-year patient (96.4%) and death-censored graft survival (96.8%) was excellent. We also found that cPRA 100% recipients had a relatively low incidence of T cell-mediated rejection (9.2%) and antibody-mediated rejection (AMR) (13.8%). T cell-mediated rejection episodes tended to be relatively mild-50% (5 episodes) were grade 1, 50% (5 episodes) were grade 2, and none were grade 3. Only 1 episode was associated with graft loss, but this was in the context of a mixed rejection. Although only 15 recipients (13.8%) developed an AMR episode, 2 of these were associated with a graft loss. Despite the rejection episodes, the vast majority of recipients had excellent graft function 3 years posttransplant (median serum creatinine 1.5 mg/dL). In conclusion, cPRA 100% DDKT recipients are doing well under KAS, although every effort should be made to prevent AMR to ensure long-term outcomes remain excellent.

BACKGROUND:One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection. METHODS:In this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per μL for liver and >200 cells per μL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262. FINDINGS:14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART. INTERPRETATION:These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients. FUNDING:US National Institute of Allergy and Infectious Diseases and National Cancer Institute.

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.