Faculty Bibliography

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.

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.

BACKGROUND:Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that antithymocyte globulin (ATG) might increase HCV-related complications. METHODS:Using Scientific Registry of Transplant Recipients and Medicare claims data, we studied 6780 HCV+ and 139 681 HCV- KT recipients in 1999-2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (versus IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (versus IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression. RESULTS:HCV+ recipients were less likely to receive ATG than HCV- recipients (living donor, adjusted odds ratio [aOR] = 0.640.770.91; deceased donor, aOR = 0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-y crude incidence = 11.6% versus 12.6%; aOR = 0.680.820.99). There was no significant difference in the risks of graft failure (adjusted hazard ratio [aHR] = 0.861.001.17), death (aHR = 0.850.951.07), liver transplant registration (aHR = 0.580.971.61), and cirrhosis (aHR = 0.730.921.16). CONCLUSIONS:Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.

BACKGROUND AND OBJECTIVES:Mortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing. RESULTS:=0.72). CONCLUSIONS:Codispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.

BACKGROUND:Given the potential utility of frailty, a clinical phenotype of decreased physiologic reserve and resistance to stressors, to predict postkidney transplant (KT) outcomes, we sought to understand the perceptions and practices regarding frailty measurement in US KT programs. METHODS:Surveys were emailed to American Society of Transplantation Kidney/Pancreas Community of Practice members and 202 US transplant programs (November 2017 to April 2018). Program characteristics were gleaned from Scientific Registry of Transplant Recipients. RESULTS:The 133 responding programs (response rate = 66%) represented 77% of adult KTs and 79% of adult KT candidates in the United States. Respondents considered frailty to be a useful concept in evaluating candidacy (99%) and endorsed a need to develop a frailty measurement specific to KT (92%). Frailty measurement was more common during candidacy evaluation (69%) than during KT admission (28%). Of the 202 programs, 38% performed frailty assessments in all candidates while 23% performed assessments only for older candidates. There was heterogeneity in the frailty assessment method; 18 different tools were utilized to measure frailty. The most common tool was a timed walk test (19%); 67% reported performing >1 tool. Among programs that measure frailty, 53% reported being less likely to list frail patients for KT. CONCLUSIONS:Among US KT programs, frailty is recognized as a clinically relevant construct and is commonly measured at evaluation. However, there is considerable heterogeneity in the tools used to measure frailty. Efforts to identify optimal measurement of frailty using either an existing or a novel tool and subsequent standardization of its measurement and application across KT programs should be considered.

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007-2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0-14 days, 15-182 days, and 183-365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, _LCL aOR_UCL ). Among 23,565 donors, opioid prescriptions were highest during days 0-14 (36.6%), but 12.6% of donors filled opioids during days 183-365. NSAID prescriptions rose from 0.5% during days 0-14 to 3.3% during days 183-365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183-365 included obesity (aOR,_1.24 1.38_1.53 ), less than college education (aOR,_1.19 1.31_1.43 ), smoking (aOR,_1.33 1.45_1.58 ), and nephrectomy complications (aOR,_1.11 1.29_1.49 ). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new-onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer-term outcome implications to help inform safe analgesic regimen choices after donation.

The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N = 98 620), and associations (adjusted hazard ratio, _LCL aHR_UCL ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, _1.08 1.22_1.38 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5 years (aHR: short-acting _1.29 1.39_1.48 ; long-acting _1.12 1.25_1.40 ; both _1.46 1.74_2.07 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.

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.

BACKGROUND:End-stage kidney disease (ESKD) patients are living longer, often into older age, and commonly pursue kidney transplantation. Successful aging, a multidimensional construct of physical and social wellbeing, has been expanded and adapted for patients with chronic disease. However, perceptions of, barriers to, and experiences with successful aging among adults with ESKD are unclear and likely differ based on whether they have received a kidney transplant. METHODS:Ten focus groups were held with 39 total ESKD patients aged ≥50 years (19 transplant candidates, 20 transplant recipients). Transcriptions were analyzed thematically by 2 independent coders using an inductive, constant comparative approach. RESULTS:The mean age was 64.8 (SD = 7.5); 51% were African American and 64% were males. Six themes were identified: familiarity with successful aging, perceptions of successful aging after ESKD diagnosis, barriers to successful aging, experiences with successful aging among transplant candidates, experiences with successful aging among transplant recipients, and suggested interventions. While all participants sought to achieve successful aging while living with ESKD, experiences with successful aging differed between candidates and recipients. Candidates struggled with the limitations of dialysis; some viewed transplantation as an opportunity to age successfully, while others were resigned to the drawbacks of dialysis. In contrast, transplant recipients were optimistic about their ability to age successfully, believing their transplant facilitated successful aging. Participants believed support groups for adults with ESKD and more thoughtful health care for aging adults would promote successful aging. CONCLUSIONS:Adults with ESKD may benefit from discussions with their clinicians and caregivers about goals, barriers, and strategies regarding successful aging.

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.