Faculty Bibliography

BACKGROUND:Patients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021. RESULTS:Rates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted. CONCLUSIONS:Two-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines.

BACKGROUND:Solid organ transplant recipients (SOTR) have diminished humoral immune responses to COVID-19 vaccination and higher rates of COVID-19 vaccine breakthrough infection than the general population. Little is known about COVID-19 disease severity in SOTR with COVID-19 vaccine breakthrough infections. METHODS:Between 4/7/21 and 6/21/21 we requested case reports via the Emerging Infections Network (EIN) listserv of SARS-CoV-2 infection following COVID-19 vaccination in SOTR. Online data collection included patient demographics, dates of COVID-19 vaccine administration and clinical data related to COVID-19. We performed a descriptive analysis of patient factors and evaluated variables contributing to critical disease or need for hospitalization. RESULTS:Sixty-six cases of SARS-CoV-2 infection after vaccination in SOTR were collected. COVID-19 occurred after the second vaccine dose in 52 (78.8%) cases of which 43 (82.7%) occurred ≥14 days post-vaccination. There were 6 deaths, 3 occurring in fully vaccinated individuals (7.0%, n = 3/43). There was no difference in the percentage of patients who recovered from COVID-19 (70.7% vs 72.2%, p = 0.90) among fully and partially vaccinated individuals. We did not identify any differences in hospitalization (60.5% vs. 55.6%, p = 0.72) or critical disease (20.9% vs. 33.3%, p = 0.30) among those who were fully vs. partially vaccinated. CONCLUSIONS:SOTR vaccinated against COVID-19 can still develop severe, and even critical, COVID-19 disease. Two doses of mRNA COVID-19 vaccine may be insufficient to protect against severe disease and mortality in SOTR. Future studies to define correlates of protection in SOTR are needed. This article is protected by copyright. All rights reserved.

BACKGROUND:Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades, but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment. METHODS:Using the SRTR and Medicare claims data, we identified 5,094 adults (age≥18) treated with cinacalcet or parathyroidectomy for SHPT prior to receiving KT between 2007-2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics. RESULTS:Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure or death. However, compared to patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (aHR=0.56, 95%CI: 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (pinteraction=0.039). Among patients on maintenance dialysis therapy for ≥3 years prior to KT (n=3,477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (aHR=0.43, 95%CI: 0.24-0.79). CONCLUSIONS:Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 years. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.

A wide gap between the increasing demand for organs and the limited supply leads to immeasurable loss of life each year. The organ shortage could be attenuated by donors with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). The transplantation of organs from HIV+ deceased donors into HIV+ individuals (HIV D+ /R+) was initiated in South Africa in 2010; however, this practice was forbidden in the USA until the HIV Organ Policy Equity (HOPE) Act in 2013. HIV D+/R+ transplantation is now practiced in the USA as part of ongoing research studies, helping to reduce waiting times for all patients on the waitlist. The introduction of direct acting antivirals for HCV has revolutionized the utilization of donors with HCV for HCV-uninfected (HCV-) recipients. This is particularly relevant as the HCV donor pool has increased substantially in the context of the rise in deaths related to drug overdose from injection drug use. This article serves to review the current literature on using organs from donors with HIV or HCV.

BACKGROUND:Kidney allograft failure is a common cause of end-stage renal disease. We aimed to develop a dynamic artificial intelligence approach to enhance risk stratification for kidney transplant recipients by generating continuously refined predictions of survival using updates of clinical data. METHODS:In this observational study, we used data from adult recipients of kidney transplants from 18 academic transplant centres in Europe, the USA, and South America, and a cohort of patients from six randomised controlled trials. The development cohort comprised patients from four centres in France, with all other patients included in external validation cohorts. To build deeply phenotyped cohorts of transplant recipients, the following data were collected in the development cohort: clinical, histological, immunological variables, and repeated measurements of estimated glomerular filtration rate (eGFR) and proteinuria (measured using the proteinuria to creatininuria ratio). To develop a dynamic prediction system based on these clinical assessments and repeated measurements, we used a Bayesian joint models-an artificial intelligence approach. The prediction performances of the model were assessed via discrimination, through calculation of the area under the receiver operator curve (AUC), and calibration. This study is registered with ClinicalTrials.gov, NCT04258891. FINDINGS/RESULTS:13 608 patients were included (3774 in the development cohort and 9834 in the external validation cohorts) and contributed 89 328 patient-years of data, and 416 510 eGFR and proteinuria measurements. Bayesian joint models showed that recipient immunological profile, allograft interstitial fibrosis and tubular atrophy, allograft inflammation, and repeated measurements of eGFR and proteinuria were independent risk factors for allograft survival. The final model showed accurate calibration and very high discrimination in the development cohort (overall dynamic AUC 0·857 [95% CI 0·847-0·866]) with a persistent improvement in AUCs for each new repeated measurement (from 0·780 [0·768-0·794] to 0·926 [0·917-0·932]; p<0·0001). The predictive performance was confirmed in the external validation cohorts from Europe (overall AUC 0·845 [0·837-0·854]), the USA (overall AUC 0·820 [0·808-0·831]), South America (overall AUC 0·868 [0·856-0·880]), and the cohort of patients from randomised controlled trials (overall AUC 0·857 [0·840-0·875]). INTERPRETATION/CONCLUSIONS:Because of its dynamic design, this model can be continuously updated and holds value as a bedside tool that could refine the prognostic judgements of clinicians in everyday practice, hence enhancing precision medicine in the transplant setting. FUNDING/BACKGROUND:MSD Avenir, French National Institute for Health and Medical Research, and Bettencourt Schueller Foundation.

BACKGROUND:While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. METHODS:US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. RESULTS:Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. CONCLUSIONS:HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18-64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59-3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33-0.41 and aHR = 0.31, 95% CI: 0.24-0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.