Faculty Bibliography

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.

In March 2020, COVID-19 infections began to rise exponentially in the United States, 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. 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 United States compared to the same time the previous year. We saw an initial decrease in DDKT and LDKT by 47% and 82% compared to expected events and then a continual increase, with numbers reaching expected pre-pandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR _0.49 0.65 _0.85 ) and LDKT (IRR _0.17 0.38 _0.84 ) _{in states with high vs low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar cPRA, waitlist time and cause of ESRD as before the pandemic. The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the United States, but has not had a sustained effect.}

An increasing number of studies claim machine learning (ML) predicts transplant outcomes more accurately. However, these claims were possibly confounded by other factors, namely, supplying new variables to ML models. To better understand the prospects of ML in transplantation, we compared ML to conventional regression in a "common" analytic task: predicting kidney transplant outcomes using national registry data. We studied 133 431 adult deceased-donor kidney transplant recipients between 2005 and 2017. Transplant centers were randomly divided into 70% training set (190 centers/97 787 recipients) and 30% validation set (82 centers/35 644 recipients). Using the training set, we performed regression and ML procedures [gradient boosting (GB) and random forests (RF)] to predict delayed graft function, one-year acute rejection, death-censored graft failure C, all-cause graft failure, and death. Their performances were compared on the validation set using -statistics. In predicting rejection, regression (C = _0.601 0.611_0.621 ) actually outperformed GB (C = _0.581 0.591_0.601 ) and RF (C = _0.569 0.579_0.589 ). For all other outcomes, the C-statistics were nearly identical across methods (delayed graft function, 0.717-0.723; death-censored graft failure, 0.637-0.642; all-cause graft failure, 0.633-0.635; and death, 0.705-0.708). Given its shortcomings in model interpretability and hypothesis testing, ML is advantageous only when it clearly outperforms conventional regression; in the case of transplant outcomes prediction, ML seems more hype than helpful.

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.

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:Live kidney donors (LKDs) account for nearly a third of kidney transplants in the United States. While donor nephrectomy poses minimal post-surgical risk, LKDs face an elevated adjusted risk of developing chronic diseases such as hypertension, diabetes, and end-stage renal disease. Routine screening presents an opportunity for the early detection and management of chronic conditions. Transplant hospital reporting requirements mandate the submission of laboratory and clinical data at 6-months, 1-year, and 2-years after kidney donation, but less than 50% of hospitals are able to comply. Strategies to increase patient engagement in follow-up efforts while minimizing administrative burden are needed. We seek to evaluate the effectiveness of using small financial incentives to promote patient compliance with LKD follow-up. METHODS/DESIGN:We are conducting a two-arm randomized controlled trial (RCT) of patients who undergo live donor nephrectomy at The Johns Hopkins Hospital Comprehensive Transplant Center (MDJH) and the University of Maryland Medical Center Transplant Center (MDUM). Eligible donors will be recruited in-person at their first post-surgical clinic visit or over the phone. We will use block randomization to assign LKDs to the intervention ($25 gift card at each follow-up visit) or control arm (current standard of care). Follow-up compliance will be tracked over time. The primary outcome will be complete (all components addressed) and timely (60 days before or after expected visit date), submission of LKD follow-up data at required 6-month, 1-year, and 2-year time points. The secondary outcome will be transplant hospital-level compliance with federal reporting requirements at each visit. Rates will be compared between the two arms following the intention-to-treat principle. DISCUSSION:Small financial incentivization might increase patient compliance in the context of LKD follow-up, without placing undue administrative burden on transplant providers. The findings of this RCT will inform potential center- and national-level initiatives to provide all LKDs with small financial incentives to promote engagement with post-donation monitoring efforts. TRIAL REGISTRATION:ClinicalTrials.gov number: NCT03090646 Date of registration: March 2, 2017 Sponsors: Johns Hopkins University, University of Maryland Medical Center Funding: The Living Legacy Foundation of Maryland.

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).

With implementation of the Kidney Allocation System, the growth of kidney paired donation programs, and advances in desensitization and immunosuppression, the outlook for "untransplantable" kidney transplantation candidates has never been more promising. The Kidney Allocation System prioritized compatible matches for candidates with calculated panel-reactive antibody levels of 98%, 99%, or 100% and broadened allocation of non-A1 and non-A1-B subgroup kidneys to blood group type B candidates. Concurrently, the growth of kidney paired donation programs and use of incompatible transplantation as part of kidney paired donation to achieve "more compatible" kidney transplantation has improved options for candidates with an incompatible living donor. Finally, advances in desensitization and immunosuppression have strengthened the ability to manage donor-specific antibodies and antibody-mediated rejection. Although no patient should be labeled "untransplantable" due to blood group type or donor-specific antibody, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers when needed. In this Perspective, we consider blood group type ABO incompatibility, HLA antigen incompatibility, antibody-mediated rejection, kidney paired donation, and recent developments in incompatible transplantation in more depth and recommend an approach to the sensitized candidate.

BACKGROUND:Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF. METHODS:We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis. RESULTS:The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001). CONCLUSIONS:In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.