Faculty Bibliography

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.

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.

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: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: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:HIV-infected (HIV+) donor to HIV+ recipient (HIV D+/R+) transplantation might improve access to transplantation for people living with HIV. However, it remains unknown whether transplant candidates living with HIV will accept the currently unknown risks of HIV D+/R+ transplantation. METHODS:We surveyed transplant candidates living with HIV from 9 US transplant centers regarding willingness to accept HIV+ donor organs. RESULTS:Among 116 participants, the median age was 55 years, 68% were men, and 78% were African American. Most were willing to accept HIV+ living donor organs (87%), HIV+ deceased donor organs (84%), and increased infectious risk donor organs (70%). Some (30%) were concerned about HIV superinfection; even among these respondents, 71% were willing to accept an HIV D+ organ. Respondents from centers that had already performed a transplant under an HIV D+/R+ transplantation research protocol were more willing to accept HIV+ deceased donor organs (89% vs. 71%, P = 0.04). Respondents who chose not to enroll in an HIV D+/R+ transplantation research protocol were less likely to believe that HIV D+/R+ transplantation was safe (45% vs. 77%, P = 0.02), and that HIV D+ organs would work similar to HIV D- organs (55% vs. 77%, P = 0.04), but more likely to believe they would receive an infection other than HIV from an HIV D+ organ (64% vs. 13%, P < 0.01). CONCLUSIONS:Willingness to accept HIV D+ organs among transplant candidates living with HIV does not seem to be a major barrier to HIV D+/R+ transplantation and may increase with growing HIV D+/R+ transplantation experience.

Simple (Bosniak I) renal cysts are considered acceptable in living kidney donor selection in terms of cancer risk. However, they tend to increase in number and size over time and might compromise renal function in donors. To clarify their implications for long-term renal function, we characterized the prevalence of renal cysts in 454 individuals who donated at our center from 2000 to 2007. We estimated the association between the presence of cysts in the kidney remaining after nephrectomy (ie, retained cysts) and postdonation eGFR trajectory using mixed-effects linear regression. Donors with retained cysts (N = 86) were older (P < .001) and had slightly lower predonation eGFR (median 94 vs 98 mL/min/1.73 m² , P < .01) than those without cysts. Over a median 7.8 years, donors with retained cysts had lower baseline eGFR (_-8.7 -5.6 _-2.3  mL/min/1.73 m² , P < .01) but similar yearly change in eGFR (_-0.4 0.02 _0.4  mL/min/1.73 m² , P = .2) compared to those without retained cysts. Adjusting for predonation characteristics, there was no difference in baseline eGFR (P = .6) or yearly change in eGFR (P > .9). There continued to be no evidence of an association when we considered retained cyst(s) ≥10 mm or multiple retained cysts (all P > .05). These findings reaffirm current practices of accepting candidates with simple renal cysts for donor nephrectomy.

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.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence. The strengths of recommendations are provided in the full report. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.