Faculty Bibliography

Implementation of the HIV Organ Policy Equity (HOPE) Act marks a new era in transplantation, allowing organ transplantation from HIV+ donors to HIV+ recipients (HIV D+/R+ transplantation). In this review, we discuss major milestones in HIV and transplantation which paved the way for this landmark policy change, including excellent outcomes in HIV D-/R+ recipient transplantation and success in the South African experience of HIV D+/R+ deceased donor kidney transplantation. Under the HOPE Act, from March 2016 to December 2018, there were 56 deceased donors, and 102 organs were transplanted (71 kidneys and 31 livers). In 2019, the first HIV D+/R+ living donor kidney transplants occurred. Reaching the full estimated potential of HIV+ donors will require overcoming challenges at the community, organ procurement organization, and transplant center levels. Multiple clinical trials are ongoing, which will provide clinical and scientific data to further extend the frontiers of knowledge in this field.

BACKGROUND:Kidney transplant recipients have higher risk of infectious diseases due to their reliance on immunosuppression. During the current COVID-19 pandemic, some clinicians might have opted for less potent immunosuppressive agents to counterbalance the novel infectious risk. We conducted a nationwide study to characterize immunosuppression use and subsequent clinical outcomes during the first 5 months of COVID-19 pandemic in the United States. METHODS:Using data from the Scientific Registry of Transplant Recipients, we studied all kidney-only recipients in the United States from January 1, 2017, to March 12, 2020 ("prepandemic" era; n = 64 849) and from March 13, 2020, to July 31, 2020 ("pandemic" era; n = 5035). We compared the use of lymphocyte-depleting agents (versus basiliximab or no induction) and maintenance steroids (versus steroid avoidance/withdrawal) in the pandemic era compared with the prepandemic era. Then, we compared early posttransplant outcomes by immunosuppression regimen during the pandemic era. RESULTS:Recipients in the pandemic era were substantially less likely to receive lymphocyte-depleting induction agents compared with their prepandemic counterparts (aOR = 0.400.530.69); similar trends were found across subgroups of state-level COVID-19 incidence, donor type, and recipient age. However, lymphocyte-depleting induction agents were associated with decreased rejection during admission (aOR = 0.110.230.47) but not with increased mortality in the pandemic era (aHR = 0.130.471.66). On the other hand, the use of maintenance steroids versus early steroid withdrawal remained similar (aOR = 0.711.071.62). CONCLUSIONS:The use of lymphocyte-depleting induction agents has decreased in favor of basiliximab and no induction during the COVID-19 pandemic. However, this shift might have resulted in increases in rejection with no clear reductions in posttransplant mortality.

BACKGROUND:Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective. METHODS:Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States. RESULTS:Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/μL. Median CD4 pre-COVID-19 was 298 cells/μL, declining to <200 cells/μl in 6/7 with measurements on admission. Treatment included high-dose steroids (n = 6), tocilizumab (n = 3), remdesivir (n = 2), and convalescent plasma (n = 2). Four patients (36%) died. CONCLUSIONS:Within a national prospective cohort of kidney and liver transplant recipients with HIV, we report high mortality from COVID-19.

BACKGROUND:In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. METHODS:Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. RESULTS:) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel-reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. CONCLUSIONS:The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect.

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P < .001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: _2.15 2.22_2.29 , P < .001) and 1.92-fold higher DCGF risk (aHR: _1.84 1.91_1.98 , P < .001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks.

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

BACKGROUND:Prior studies demonstrated that older adults tend to undergo less surgery for thyroid cancer. Our objective was to use a discrete choice experiment to identify factors influencing surgical decision-making for older adults with thyroid cancer. METHODS:Active and candidate members of the American Association of Endocrine Surgeons were invited to participate in a web-based survey. Multinomial logistic regression was utilized to assess patient and surgeon factors associated with treatment choices. RESULTS:Complete survey response rate was 25.7%. Most respondents were high-volume surgeons (88.5%) at academic centers (76.9%). Multinomial logistic regression demonstrated that patient age was the strongest predictor of management. Increasing age and comorbidities were associated with the choice for active surveillance (P = .000), not performing a lymphadenectomy in patients with nodal metastases (relative-risk ratio: 2.5, 95% CI: 1.4-4.2, P = .002 and relative-risk ratio: 1.6, 95% CI: 1.2-2.1, P = .004, respectively), and recommending hemithyroidectomy versus total thyroidectomy for a cancer >4 cm (relative-risk ratio: 4.4, 95% CI: 2.5-7.9, P = .000 and relative-risk ratio: 3.4, 95% CI: 2.3-5.1, P = .000, respectively). Surgeons with ≥10 years of experience (relative-risk ratio: 3.3, 95% CI: 1.1-10.3, P = .039) favored total thyroidectomy for a cancer <4 cm, and nonfellowship trained surgeons (relative-risk ratio: 7.3, 95% CI: 1.3-42.2, P = .027) opted for thyroidectomy without lymphadenectomy for lateral neck nodal metastases. CONCLUSION:This study highlights the variation in surgical management of older adults with thyroid cancer and demonstrates the influence of patient age, comorbidities, surgeon experience, and fellowship training on management of this population.