Faculty Bibliography

BACKGROUND:Optimizing amino acid (eplet) histocompatibility at first transplant decreases the risk of de novo donor-specific antibody (dnDSA) development and may improve long-term graft survival in pediatric kidney transplant recipients (KTR). We performed a retrospective analysis of pediatric KTR and their respective donors to identify eplets most commonly associated with dnDSA formation. METHODS:Eplet mismatch analysis was performed in a cohort of 125 pediatric KTR-donor pairs (2006-2018). We determined the prevalence of each eplet mismatch and quantified the percentage of exposed patients who developed dnDSA for each mismatched eplet. RESULTS:Recipient median age was 14 (IQR 8-17) years with a racial distribution of 42% Black, 48% Caucasian, and 5.6% Middle-Eastern. Median eplet load varied significantly by recipient race, Black 82 (IQR 58-98), White 60 (IQR 44-81) and Other 66 (IQR 61-76), p = 0.002. Forty-four percent of patients developed dnDSA after median 37.1 months. Compared to dnDSA- patients, dnDSA+ patients had higher median eplet load, 64 (IQR 46-83) vs. 77 (IQR 56-98), p = 0.012. The most common target of dnDSA were eplets expressed in HLA-A*11 and A2 in Class I, and HLA-DQ6 and DQA5 in Class II. The most commonly mismatched eplets were not the most likely to result in dnDSA formation. CONCLUSIONS:In a racially diverse population, only a subset of eplets was linked to antibody formation. Eplet load alone is not a sufficient surrogate for eplet immunogenicity. These findings illustrate the need to optimize precision in donor selection and allocation to improve long-term graft outcomes. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

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 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 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).

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.

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.