Sociodemographic disparities in sodium-glucose cotransporter-2 inhibitor use among US kidney transplant recipients: An observational study of real-world pharmacy records.

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.

Statins in Kidney Transplant Recipients: Usage, All-Cause Mortality, and Interactions with Maintenance Immunosuppressive Agents.

SIGNIFICANCE STATEMENT: Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND: Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS: We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS: Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION: Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression.

Biliary Complications After Liver Transplantation in the United States: Changing Trends and Economic Implications.

BACKGROUND: Biliary complications (BCs) continue to impact patient and graft survival after liver transplant (LT), despite improvements in organ preservation, surgical technique, and posttransplant care. Real-world evidence provides a national estimate of the incidence of BC after LT, implications for patient and graft outcomes, and attributable cost not available in transplant registry data. METHODS: An administrative health claims-based BC identification algorithm was validated using electronic health records (N = 128) and then applied to nationally linked Medicare and transplant registry claims. RESULTS: The real-world evidence algorithm identified 97% of BCs in the electronic health record review. Nationally, the incidence of BCs within 1 y of LT appears to have improved from 22.2% in 2002 to 20.8% in 2018. Factors associated with BCs include donor type (living versus deceased), recipient age, diagnosis, prior transplant, donor age, and donor cause of death. BCs increased the risk-adjusted hazard ratio (aHR) for posttransplant death (aHR, 1.43; P < 0.0001) and graft loss (aHR, 1.48; P < 0.0001). Nationally, BCs requiring intervention increased risk-adjusted first-year Medicare spending by $39 710 ( P < 0.0001). CONCLUSIONS: BCs remain an important cause of morbidity and expense after LT and would benefit from a systematic quality-improvement program.

Incidence of Statin-Associated Adverse Events in Kidney Transplant Recipients.

BACKGROUND: Statins are the third most prescribed drug class in kidney transplant recipients as cardiovascular diseases is the leading cause of death in this population. However, statins' safety profile remains unclear in kidney transplant recipients who are uniquely burdened by concomitant immunosuppression and comorbidities. We conducted a national study to characterize the association of statin use with adverse events in kidney transplant recipients. METHODS: We studied adult (≥18) single-organ kidney transplant recipients in 2006-2016 with Medicare as primary payer (n=57,699). We used prescription drug claims to capture statin use, and ICD-9/10 diagnosis codes to capture statin-related adverse events (post-transplant diabetes mellitus, hemorrhagic stroke, cataract, liver injury, and rhabdomyolysis). We conducted multivariable Cox regression for each outcome with statin use as a time-varying exposure. RESULTS: Post-transplant diabetes mellitus was the most common outcome (5-year Kaplan-Meier incidence; 43% in statin users vs. 35% in non-users), followed by cataract (22% vs. 12%), liver injury (2% vs. 3%), hemorrhagic stroke (1.9% vs. 1.4%), and rhabdomyolysis (1.5% vs. 0.9%). In our multivariable analysis, statin use was associated with higher hazard of post-transplant diabetes mellitus (aHR=1.12 [95% CI, 1.07-1.18]), cataract (aHR=1.22 [1.14-1.31]), and rhabdomyolysis (aHR=1.37 [1.10-1.71]), but lower hazard of liver injury (aHR=0.82 [0.71-0.95]). Statin use was not associated with hemorrhagic stroke (aHR=1.04 [0.86-1.26]). CONCLUSIONS: Statins appear to be generally well-tolerated in kidney transplant recipients. However, statin use might be associated with slightly higher risk of post-transplant diabetes mellitus, cataract, and rhabdomyolysis.

Variation in adult living donor liver transplantation in the United States: Identifying opportunities for increased utilization.

In the United States, living donor liver transplantation (LDLT) is limited to transplant centers with specific experience. However, the impact of recipient characteristics on procedure selection (LDLT vs. deceased donor liver transplant [DDLT]) within these centers has not been described. Transplant registry data for centers that performed ≥1 LDLT in 2002-2019 were analyzed using hierarchal regression modeling to quantify the impact of patient and center factors on the adjusted odds ratio (aOR) of LDLT (vs DDLT). Among 73,681 adult recipients, only 4% underwent LDLT, varying from <1% to >60% of total liver transplants. After risk adjustment, the likelihood of receiving an LDLT rose by 73% in recent years (aOR 1.73 for 2014-2019 vs. 2002-2007) but remained lower for older adults, men, racial and ethnic minorities, and obese patients. LDLT was less commonly used in patients with hepatocellular carcinoma or alcoholic cirrhosis, and more frequently in those with hepatitis C and with lower severity of illness (Model for End-Stage Liver Disease (MELD) score < 15). Patients with public insurance, lower educational achievement, and residence in the Northwest and Southeast had decreased access. While some differences in access to LDLT reflect clinical factors, further exploration into disparities in LDLT utilization based on center practice and socioeconomic determinants of health is needed.

Impact of CYP3A5 Status on the Clinical and Financial Outcomes Among African American Kidney Transplant Recipients.

Pharmacogenetic profiling of transplant recipients demonstrates that the marked variation in the metabolism of immunosuppressive medications, particularly tacrolimus, is related to genetic variants. Patients of African ancestry are less likely to carry loss-of-function (LoF) variants in the CYP3A5 gene and therefore retain a rapid metabolism phenotype and higher clearance of tacrolimus. Patients with this rapid metabolism typically require higher dosing to achieve therapeutic trough concentrations. This study aims to further characterize the impact of CYP3A5 genotype on clinical outcomes and financial expenditure. Methods: The CYP3A5 phenotype status was identified in 438 adult kidney transplant (KTx) recipients (96% were African American) using 3 LoF alleles (CYP3A5*3, *6 or *7). Individuals were categorized as rapid metabolism phenotype without LoF alleles' intermediate phenotype for 1 LoF allele' and slow phenotype for 2 LoF alleles. KTx outcomes (patient/kidney survival and Medicare spending) were determined using linked transplant registry and claims data. Results: Among the cohort, 23% had a rapid, 47% intermediate, and 30% a slow metabolism phenotype based on genotype. At 3 y, the rate of death censored graft failure and all cause graft failure was highest in the rapid metabolism phenotype and lowest in the intermediate metabolism phenotype group. First-year Medicare reimbursement differed significantly by genotype (rapid: $79 535, intermediate: $72 796, slow: $79 346, P = 0.03). After adjustment for donor and recipient characteristics, care for patients with intermediate metabolism was $4790 less expensive (P = 0.003). Conclusions: Pharmacogenomic assessment of African American KTx recipients may be useful to guide therapy when as CYP3A5 functional variants appear to be associated with differential outcome and spending after transplant.

The need for integrated clinical and administrative data models for risk adjustment in assessment of the cost transplant care.

INTRODUCTION: Value-based purchasing requires accurate techniques to appropriately measure both outcomes and cost with robust adjustment for differences in severity of illness. Traditional methods to adjust cost estimates have exclusively used administrative data derived from billing claims to identify comorbidity and complications. Transplantation uniquely has accurate national clinical registry data that can be used to supplement administrative data. METHODS: Administrative claims from the Vizient, Inc, Clinical Data Base (CDB) were linked with clinical records from the Scientific Registry for Transplant Recipients for 76 liver and 109 kidney transplant programs. Using either or both datasets, we fitted a regression model to the total direct cost of care for 16,649 kidney and 6058 liver transplants. RESULTS: The proportion of variation explained by these risk-adjustment models increased significantly when combined administrative and clinical data were used for kidney (administrative only R2 = .069, clinical only R2 = .047, combined R2 = .14, p < .0001) and liver (administrative only R2 = .28, clinical only R2 = .25, combined R2 = .33, p < .0001). CONCLUSION: Incorporating accurate clinical data into risk-adjustment methodologies can improve risk adjustment methodologies; however, as majority of variation in cost remains unexplained by these risk-adjustment models further work is needed to accuracy assess transplant value.

Exacerbation of Racial Disparities in Living Donor Kidney Transplantation During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic profoundly impacted transplant services, with a particularly strong impact on living donor kidney transplantation.The COVID-19 pandemic appears to have disproportionately impacted Black patients' access to living donor kidney transplantation.As the pandemic evolves through surges and vaccine acceptance disparities persist, ongoing attention to transplant disparities is needed.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications.

Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Deceased Donor Procurement Biopsy Practices, Interpretation, and Histology-Based Decision-Making: A Survey of US Kidney Transplant Centers.

Introduction: The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts. Methods: An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices. Results: Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney. Conclusion: Procurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.

Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients.

RATIONALE & OBJECTIVE: Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. STUDY DESIGN: Retrospective database study. SETTING & PARTICIPANTS: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. EXPOSURES: Various immunosuppression regimens in the first 3 months after transplant. OUTCOMES: Development of DM >3 months-to-1 year posttransplant. ANALYTICAL APPROACH: We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. RESULTS: 12.7% of kidney transplant recipients developed posttransplant DM with higher incidences in older (≥55 years vs <55 years: 16.7% vs 10.1%) and obese (body mass index [BMI] ≥ 30 kg/m2 vs BMI < 30 kg/m2: 17.1% vs 10.9%) patients. The incidence of posttransplant DM was lower with steroid avoidance [TMG/ALEM + no prednisone (8.4%) and IL2rAb + no prednisone (9.7%)] than TMG/ALEM with triple therapy (13.1%). After adjustment for donor and recipient characteristics, TMG/ALEM with steroid avoidance was beneficial for all groups [age < 55 years: adjusted HR (aHR), 0.63 (95% confidence interval [CI], 0.54-0.72); age ≥ 55 years: aHR, 0.69 (95% CI, 0.60-0.79); BMI < 30 kg/m2: aHR, 0.69 (95% CI, 0.60-0.78); BMI ≥ 30 kg/m2: aHR, 0.67 (95% CI, 0.57-0.79)]. However, IL2rAb with steroid avoidance was beneficial only for older patients (aHR, 0.76; 95% CI, 0.58-0.99) and for those with BMI < 30 kg/m2 (aHR, 0.63; 95% CI, 0.46-0.87). LIMITATIONS: Retrospective study and lacked data on immunosuppression levels. CONCLUSIONS: The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

The Clinical and Economic Benefit of CMV Matching in Kidney Transplant: A Decision Analysis.

BACKGROUND: The development of cytomegalovirus (CMV) infection after kidney transplant remains a significant cause of posttransplant morbidity, graft loss, and mortality. Despite appropriate antiviral therapy, recipients without previous CMV exposure can currently be allocated a kidney from a donor with previous CMV infection (D+R-) that carries the greatest risk of posttransplant CMV infection and associated complications. Preferential placement of CMV D- organs in negative recipients (R-) has been shown to reduce the risk of viral infection and associated complications. METHODS: To assess the long-term survival and economic benefits of allocation policy reforms, a decision-analytic model was constructed to compare receipt of CMV D- with CMV D+ organ in CMV R- recipients using data from transplant registry, Medicare claims, and pharmaceutical costs. RESULTS: For CMV R- patients, receipt of a CMV D- organ was associated with greater average survival (14.3 versus 12.6 y), superior quality-adjusted life years (12.6 versus 9.8), and lower costs ($529 512 versus $542 963). One-way sensitivity analysis demonstrated a survival advantage for patients waiting as long as 30 mo for a CMV D- kidney. CONCLUSIONS: Altering national allocation policy to preferentially offer CMV D- organs to CMV R- recipients could improve survival and lower costs after transplant if appropriately implemented.

Incidence, Clinical Correlates, and Outcomes of Pulmonary Hypertension After Kidney Transplantation: Analysis of Linked US Registry and Medicare Billing Claims.

BACKGROUND: The incidence, risks, and outcomes associated with pulmonary hypertension (P-HTN) in the kidney transplant (KTx) population are not well described. METHODS: We linked US transplant registry data with Medicare claims (2006-2016) to investigate P-HTN diagnoses among Medicare-insured KTx recipients (N = 35 512) using billing claims. Cox regression was applied to identify independent correlates and outcomes of P-HTN (adjusted hazard ratio [aHR] 95%LCLaHR95%UCL) and to examine P-HTN diagnoses as time-dependent mortality predictors. RESULTS: Overall, 8.2% of recipients had a diagnostic code for P-HTN within 2 y preceding transplant. By 3 y posttransplant, P-HTN was diagnosed in 10.310.6%11.0 of the study cohort. After adjustment, posttransplant P-HTN was more likely in KTx recipients who were older (age ≥60 versus 18-30 y a HR, 1.912.403.01) or female (aHR, 1.151.241.34), who had pretransplant P-HTN (aHR, 4.384.795.24), coronary artery disease (aHR, 1.051.151.27), valvular heart disease (aHR, 1.221.321.43), peripheral vascular disease (aHR, 1.051.181.33), chronic pulmonary disease (aHR, 1.201.311.43), obstructive sleep apnea (aHR, 1.151.281.43), longer dialysis duration, pretransplant hemodialysis (aHR, 1.171.371.59), or who underwent transplant in the more recent era (2012-2016 versus 2006-2011: aHR, 1.291.391.51). Posttransplant P-HTN was associated with >2.5-fold increased risk of mortality (aHR, 2.572.843.14) and all-cause graft failure (aHR, 2.422.642.88) within 3 y posttransplant. Outcome associations of newly diagnosed posttransplant P-HTN were similar. CONCLUSIONS: Posttransplant P-HTN is diagnosed in 1 in 10 KTx recipients and is associated with an increased risk of death and graft failure. Future research is needed to refine diagnostic, classification, and management strategies to improve outcomes in KTx recipients who develop P-HTN.

COVID-19 vaccination timing and kidney transplant waitlist management: An international perspective.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs worldwide. The aim of this study is to assess an international perspective on challenges faced by kidney transplant programs. METHODS: We administered an electronic survey instrument from January 3, 2021 to June 8, 2021 to staff at transplant programs outside the United States that comprised of 10 questions addressing the management of kidney transplant candidates with asymptomatic COVID-19 infection or unvaccinated who receive an organ offer. RESULTS: Respondents (n = 62) represented 19 countries in five continents. Overall, 90.3% of respondents encourage vaccination on the waiting list and prior to planned living donor transplant. Twelve percent of respondents reported that they have decided to inactivate unsensitized candidates (calculated panel reactive antibody, cPRA <80%) until they received the two doses of vaccination, and 7% report inactivating candidates who have received their first vaccine dose pending receipt of their second dose. The majority (88.5%) of international respondents declined organs for asymptomatic, nucleic acid testing (NAT)+ patients during admission without documented prior infection. However, 22.9% of international respondents proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. CONCLUSIONS: Practitioners in some countries are less willing to accept deceased donor organs for waitlist candidates with incomplete COVID-19 vaccination status and to wait longer before scheduling living donor transplant, compared to United States practices. Access to vaccinations and other resources may contribute to these differences. More research is needed to guide the optimal approach to vaccination before and after transplant.

Disparities in Deceased Organ Donor Research Authorization: Experience at One Organ Procurement Organization and Call for National Conversations.

INTRODUCTION: Research with deceased donor organs can provide an important platform for studying interventions to improve organ use and outcomes after authorization from the next-of-kin (NOK) or before death by the decedent (i.e., first-person authorization [FPA]). To date, information on authorization rates across donor subgroups is lacking. METHODS: We performed a retrospective chart review of all 690 deceased organ donors from January 2017 to December 2019 at a midsized Midwestern organ procurement organization (OPO). Multivariable logistic regression was used to assess associations between donor factors and research decline (adjusted odds ratio [aOR], 95% confidence interval [CI]). RESULTS: Electronic records for all 690 deceased donors were reviewed. Of these, 659 (95.5%) yielded at least one transplanted organ. Overall, research was declined in 10.8% of donations. Compared to White donors, research decline was higher for Black (16.0% vs. 8.9%; aOR, 1.87; 95% CI, 1.03-3.40; P = 0.04) and other non-White donors (24.0% vs. 8.9%; aOR, 4.21; 95% CI, 1.02-17.39; P = 0.05). Unadjusted research decline trended higher for Hispanic donors versus non-Hispanic donors (23.1% vs. 10.5%; P = 0.14). Compared to donors age <40 years, research decline trended higher for donors age ≥65 years (16.7% vs. 11.8%; aOR, 4.87; 95% CI, 1.12-21.05; P = 0.03), whereas research decline was 55% lower when donors provided FPA (7.3% vs 15.0%; aOR, 0.45; 95% CI, 0.27-0.76; P = 0.003). CONCLUSIONS: Deceased donor research authorization decline is higher for Black, other non-White, and older donors, but lower when the descendent provides FPA. Identification of disparities in research authorization may stimulate educational strategies to reduce barriers to scientific investigations directed at optimizing the outcomes of organ donation.

Operational challenges in the COVID-19 era: Asymptomatic infections and vaccination timing.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid testing (NAT) for SARS-CoV-2 is unclear, as this result may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of robust outcomes data, transplant professionals at US adult kidney transplant centers were surveyed (February 13, 2021 to April 29, 2021) to determine community practice (N: 92 centers, capturing 41% of centers and 57% of transplants performed). The majority (97%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 32% of centers proceed with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with kidney transplant in patients with positive SARS-CoV-2 NAT results due to presumed viral shedding. Furthermore, few centers are requiring COVID-19 vaccination prior to transplantation at this time.

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

BACKGROUND: Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described. METHODS: We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung transplant (2006-2017), with risk-adjusted posttransplant survival (adjusted hazard ratio, LCLaHRUCL). RESULTS: Among 11,568 recipients, 33.7% filled an opioid prescription, and 25.8% filled a benzodiazepine prescription before transplant. Compared to patients without prescriptions, those who filled both short- and long-acting benzodiazepine prescriptions before transplant had 2-fold higher mortality in the first year posttransplant (aHR, 1.392.123.21), after adjustment for baseline factors and opioid fills, while pretransplant opioid fills were not associated with posttransplant mortality after adjustment for benzodiazepine fills. Pretransplant opioid and benzodiazepine use strongly predicted more use after transplant. Fills of both short- and long-acting benzodiazepines in the first year posttransplant were associated with 77% increased mortality >1-to-2 years posttransplant (aHR, 1.061.772.96). Compared with no posttransplant opioid fills, there was a dose-dependent association between first-year opioid fills and subsequent adjusted mortality risk (level 2: aHR, 1.171.501.92 to level 4: aHR, 1.562.012.59). These effects were independent, and interactions were not detected. CONCLUSIONS: Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.

COVID-19 test result reporting for deceased donors: Emergent policies, logistical challenges, and future directions.

The coronavirus disease 2019 (COVID-19) pandemic poses unprecedented challenges to the transplant community, including organ procurement organizations (OPOs), transplant centers, regulatory agencies, and recipient candidates. Access to timely, accurate information on the status of deceased donor viral infection is essential in determining organ acceptance. The Organ Procurement and Transplantation Network expeditiously added fields to collect these data; however, use of the data collection fields was not uniform nationally. Standardized, field-defined data capture and reporting are vital to ensure optimal organ utilization during this pandemic, and to prepare the community for subsequent challenges.

Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States.

BACKGROUND AND OBJECTIVES: Kidneys from hepatitis C virus (HCV) viremic donors have become more commonly accepted for transplant, especially after effective direct-acting antiviral therapy became available in 2014. We examined the contemporary trend of kidney discard from donors with HCV seropositivity and viremia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the Organ Procurement and Transplantation Network were used to identify deceased donor kidneys recovered for transplant. The exposure was donor HCV antibody status in the first analyses, and donor HCV antibody and viremia status in the second analyses. Multilevel, multivariable logistic regression was used to assess the association of these HCV exposure measures with kidney discard, adjusted for donor characteristics. Multilevel analyses were conducted to account for similar kidney discard pattern within clusters of organ procurement organizations and regions. RESULTS: Among 225,479 kidneys recovered from 2005 to 2019, 5% were from HCV seropositive donors. Compared with HCV seronegative kidneys, the odds of HCV seropositive kidney discard gradually declined, from a multivariable-adjusted odds ratio (aOR) of 7.06 (95% confidence interval [95% CI], 5.65 to 8.81) in 2014, to 1.20 (95% CI, 1.02 to 1.42) in 2019. Among 82,090 kidneys with nucleic acid amplification test results in 2015-2019, 4% were from HCV viremic donors and 2% were from aviremic seropositive donors. Compared with HCV aviremic seronegative kidneys, the odds of HCV viremic kidney discard decreased from an aOR of 4.89 (95% CI, 4.03 to 5.92) in 2018, to 1.48 (95% CI, 1.22 to 1.81) in 2019. By 2018 and 2019, aviremic seropositive status was not associated with higher odds of discard (2018: aOR, 1.13; 95% CI, 0.88 to 1.45; and 2019: aOR, 0.97; 95% CI, 0.76 to 1.23). CONCLUSIONS: Despite the decrease in kidney discard in recent years, kidneys from viremic (compared with aviremic seronegative) donors still had 48% higher odds of discard in 2019. The potential of these discarded organs to provide successful transplantation should be explored.

Reducing Kidney Discard With Artificial Intelligence Decision Support: the Need for a Transdisciplinary Systems Approach.

PURPOSE OF REVIEW: A transdisciplinary systems approach to the design of an artificial intelligence (AI) decision support system can more effectively address the limitations of AI systems. By incorporating stakeholder input early in the process, the final product is more likely to improve decision-making and effectively reduce kidney discard. RECENT FINDINGS: Kidney discard is a complex problem that will require increased coordination between transplant stakeholders. An AI decision support system has significant potential, but there are challenges associated with overfitting, poor explainability, and inadequate trust. A transdisciplinary approach provides a holistic perspective that incorporates expertise from engineering, social science, and transplant healthcare. A systems approach leverages techniques for visualizing the system architecture to support solution design from multiple perspectives. SUMMARY: Developing a systems-based approach to AI decision support involves engaging in a cycle of documenting the system architecture, identifying pain points, developing prototypes, and validating the system. Early efforts have focused on describing process issues to prioritize tasks that would benefit from AI support.