Faculty Bibliography

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,_1.12 1.96_3.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,_1.00 1.81_3.29 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,_1.02 1.54_2.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,_1.03 1.31_1.68 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.

Purpose of Review/UNASSIGNED:To summarize the research on effective interventions for preserving cognitive function and prevent cognitive decline in patients with end-stage kidney disease (ESKD) who are undergoing dialysis and/or kidney transplantation (KT). Recent Findings/UNASSIGNED:Among ESKD patients undergoing hemodialysis, exercise training has been administered through home-based and intradialytic interventions. Additionally, one pilot study identified intradialytic cognitive training, electronic brain games, as an intervention to preserve cognitive function among patients undergoing hemodialysis. Fewer studies have investigated interventions to preserver cognitive function among KT recipients. To date, the only randomized controlled trial in this population identified B-vitamin supplements as an intervention to preserve cognitive function. The evidence from these trials support a short-term benefit of cognitive and exercise training as well as B-vitamin supplementation among patients with ESKD. Future studies should: 1) replicate these findings, 2) identify interventions specific to KT candidates, and 3) investigate the synergistic impact of both cognitive and exercise training. Summary/UNASSIGNED:Cognitive prehabilitation, with cognitive and/or exercise training, may be novel interventions for KT candidates that not only reduces delirium risk and long-term post-KT cognitive decline but also prevents dementia.

The framework currently used for living kidney donor selection is based on estimation of acceptable donor risk, under the premise that benefits are only experienced by the recipient. However, some interdependent donors might experience tangible benefits from donation that cannot be considered in the current framework (ie, benefits experienced directly by the donor that improve their daily life, well-being, or livelihood).

BACKGROUND:Older (≥65) KT recipients differ from their younger counterparts in their immune response to immunosuppression (IS) and may have a different risk of malignancy after receiving induction. METHODS:We identified 66 700 adult KT recipients treated with anti-thymocyte globulin (ATG) (n = 40 443) or interleukin-2 receptor antagonist (IL-2RA) (n = 26 327) induction (1/1/1999-12/31/2014) using USRDS/Medicare data. We estimated the risk of first-diagnosed post-KT malignancy associated with induction (ATG vs. IL-2RA) using Cox proportional hazard models. We then tested whether these risks differed between older and younger recipients (Wald test for interaction). Models incorporated inverse probability of treatment weights to adjust for confounders. RESULTS: = 0.01) between younger (HR = 1.18; 95%CI:1.08-1.29) and older (HR = 1.01; 95%CI:0.93-1.09) recipients. CONCLUSIONS:Compared with IL-2RA induction, ATG was associated with elevated post-KT malignancy risk but only among younger recipients. Transplant centers may need to tailor induction IS for younger recipients to mitigate malignancy risk.

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.

We surveyed US transplant centers to assess practices regarding the evaluation and selection of living kidney donors based on metabolic, cardiovascular, and substance use risk factors. Our companion article describes renal aspects of the evaluation. Response rate was 31%. Compared with 2005, programs have become more accepting of hypertensive candidates: 65% in 2017% vs 41% in 2005 consider candidates with hypertension well controlled with 1 medication. One notable exception is black hypertensive candidates, who are frequently excluded regardless of severity. The most common body mass index (BMI) cutoff remains 35 kg/m² , and fewer programs now consider candidates with BMI >40 kg/m² . A 2-hour oral glucose tolerance test of ≥140 mg/dL remains the most common criterion for exclusion of prediabetic candidates. One quarter to one third of programs exclude based on isolated cardiac abnormalities, such as mild aortic stenosis; a similar proportion consider these candidates only if older than 50 years. Cigarette or marijuana smoking are infrequently criteria for exclusion, although 45% and 37% programs, respectively, require cessation 4 weeks prior to surgery. In addition to providing an overview of current practices in living kidney donor evaluation, our study highlights the importance of research evaluating outcomes with various comorbidities to guide practice.