Faculty Bibliography

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.

Clinical decision-making in kidney transplant (KT) during the coronavirus disease 2019 (COVID-19) pandemic is understandably a conundrum: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. To quantify the benefit/harm of KT in this context, we conducted a simulation study of immediate-KT vs delay-until-after-pandemic for different patient phenotypes under a variety of potential COVID-19 scenarios. A calculator was implemented (http://www.transplantmodels.com/covid_sim), and machine learning approaches were used to evaluate the important aspects of our modeling. Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority when modeling deceased donor KT) had greatest influence on benefit/harm. In most scenarios of COVID-19 dynamics and patient characteristics, immediate KT provided survival benefit; KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (eg, ≥50% fatality) than for waitlist registrants. Our simulations suggest that KT could be beneficial in many centers if local resources allow, and our calculator can help identify patients who would benefit most. Furthermore, as the pandemic evolves, our calculator can update these predictions.

Many deceased-donor and living-donor kidney transplants (KTs) rely on commercial airlines for transport. However, the coronavirus-19 pandemic has drastically impacted the commercial airline industry. To understand potential pandemic-related disruptions in the transportation network of kidneys across the United States, we used national flight data to compare scheduled flights during the pandemic vs 1-year earlier, focusing on Organ Procurement Organization (OPO) pairs between which kidneys historically most likely traveled by direct flight (High Volume by direct Air transport OPO Pairs, HVA-OPs). Across the United States, there were 39% fewer flights in April 2020 vs April 2019. Specific to the kidney transportation network, there were 65.1% fewer flights between HVA-OPs, with considerable OPO-level variation (interquartile range [IQR] 54.7%-75.3%; range 0%-100%). This translated to a drop in median number of flights between HVA-OPs from 112 flights/wk in April 2019 to 34 in April 2020 (P < .001), and a rise in wait time between scheduled flights from 1.5 hours in April 2019 (IQR 0.76-3.3) to 4.9 hours in April 2020 (IQR 2.6-11.2; P < .001). Fewer flights and longer wait times can impact logistics as well as cold ischemia time; our findings motivate an exploration of creative approaches to KT transport as the impact of this pandemic on the airline industry evolves.

BACKGROUND:Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS:We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS:Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS:In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

In light of changes in donor/recipient case-mix and increased cold ischemia times under the Kidney Allocation System (KAS), there is some concern that cPRA 100% recipients might be doing poorly under KAS. We used granular, single-center data on 109 cPRA 100% deceased donor kidney transplant (DDKT) recipients to study post-KAS posttransplant outcomes not readily available in national registry data. We found that 3-year patient (96.4%) and death-censored graft survival (96.8%) was excellent. We also found that cPRA 100% recipients had a relatively low incidence of T cell-mediated rejection (9.2%) and antibody-mediated rejection (AMR) (13.8%). T cell-mediated rejection episodes tended to be relatively mild-50% (5 episodes) were grade 1, 50% (5 episodes) were grade 2, and none were grade 3. Only 1 episode was associated with graft loss, but this was in the context of a mixed rejection. Although only 15 recipients (13.8%) developed an AMR episode, 2 of these were associated with a graft loss. Despite the rejection episodes, the vast majority of recipients had excellent graft function 3 years posttransplant (median serum creatinine 1.5 mg/dL). In conclusion, cPRA 100% DDKT recipients are doing well under KAS, although every effort should be made to prevent AMR to ensure long-term outcomes remain excellent.

BACKGROUND:The growth of the aging population coupled with the increasing incidence of thyroid cancer warrants a better understanding of thyroid cancer in older adults. We aimed to investigate the variation of treatment patterns and determine if the extent of surgery is associated with disease-specific mortality in older adults with differentiated thyroid cancer (DTC). METHODS:We performed a population-based study using the Surveillance, Epidemiology, and End Results 18 program to examine patients diagnosed with DTC between 2004 and 2015. Patients were stratified by age: younger adults (aged 18-54 y), middle adults (aged 55-64 y), older adults (aged 65-79 y), and super elderly (aged ≥80 y). Disease-specific mortality was estimated using Kaplan-Meier curves and compared using the log-rank test. Multivariable Cox regression was used to assess associations between clinicopathologic characteristics and treatment patterns on disease-specific mortality. RESULTS:Of 117,098 patients with DTC, 72,368 were younger adults, 23,726 middle adults, 18,119 older adults, and 2885 were super elderly. In patients with DTC, compared with younger adults, fewer middle, older, and super elderly adults underwent any surgery (99.0%, 98.4%, 97.4%, and 89.1%, respectively; P < 0.001) or received radioactive iodine (RAI; 48.7%, 42.5%, 39.7%, and 30.7%, respectively; P < 0.001). Furthermore, middle, older, and super elderly adults had higher risk of mortality from DTC (hazard ratio [HR]: 4.0, 95% confidence interval [CI]: 3.2-4.8, P < 0.001; HR: 7.6, 95% CI: 6.3-9.1, P < 0.001; and HR: 17.2, 95% CI: 13.8-21.3, P < 0.001, respectively). On multivariable Cox regression while adjusting for clinicopathologic confounders, management was a significant prognostic factor (no surgery HR: 3.8, 95% CI: 3.1-4.6, P < 0.001; and RAI HR: 0.7, 95% CI: 0.6-0.8, P < 0.001). CONCLUSIONS:In patients with DTC, fewer older adults (≥65 y) underwent surgery or treatment with RAI, and this was associated with a worse disease-specific survival. Surgical decision-making in the older population is complex, and future prospective studies are needed to assess this age-related treatment variation.

Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver-kidney (SLK) transplantation remains unclear, but small single-center reports have shown success with steroid-sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus-based regimens at 1 year post-transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid-sparing regimens increased post-transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi-level logistic regression modeling, we found center-level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%-53.0%). In multivariate analysis, use of a steroid-sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid-containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid-sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.

Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all-payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454-10 202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.

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.}

BACKGROUND:Kidney disease and dialysis significantly impact cognitive function across the age spectrum. Cognitive training (CT) and/or exercise training (ET) are promising approaches to preserve cognitive function among community-dwelling older adults, but have not been tested for cognition preservation in hemodialysis patients of all ages. In this manuscript, we summarize the protocol for the Interventions Made to Preserve Cognitive Function Trial (IMPCT). METHODS:We will perform a 2 × 2 factorial randomized controlled trial (RCT) of eligible adult (≥18 years) hemodialysis initiates (n = 200) to test whether intradialytic CT (brain games on a tablet PC), ET (foot peddlers) and combined CT + ET while undergoing hemodialysis preserves executive function compared to standard of care (SC). Participants will engage in the interventions to which they are randomized for 6 months. The primary objective is to compare, among interventions, the 3-month change in executive function measured using the Trail Making Test A (TMTA) and B (TMTB); specifically, executive function is calculated as TMTB-TMTA to account for psychomotor speed. This primary outcome was selected based on findings from our pilot study. The secondary objectives are to compare the risk of secondary cognitive outcomes, ESKD-specific clinical outcomes, and patient-centered outcomes at 3-months and 6-months. All data collection and interventions are conducted in the dialysis center. DISCUSSION:We hypothesize that receiving intradialytic CT or ET will better preserve executive function than SC but receiving combined CT + ET, will be the most effective intervention. The current trial will be an important step in understanding how intradialytic interventions might preserve cognitive health. TRIAL REGISTRATION:Clinicaltrials.Gov (Date: 8/6/18): # NCT03616535 . Protocol Version: 10 (April 2020). FUNDING:NIDDK R01DK114074.