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.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

The Effect of a Merit Point Incentive System on the Willingness to Donate Organs.

PURPOSE: Although over 90% of the population of the United States supports organ donation, only 60% of the population is registered as donors. Currently, there is a need for a nonmonetary incentive that will improve willingness to donate. We assessed the young adult population's perspective on their willingness to donate organs when merit points are granted to their family members to prioritize their potential transplant if needed. METHODS: We administered a Qualtrics survey from March 2022 to September 2022 to the undergraduate students volunteering to participate at Saint Louis University, which comprised 10 questions that addressed the attitudes of participants regarding the effects of various factors, including the type of donation and the presence of merit points (vouchers granted to self or a family member to facilitate a potential transplant if needed), on participant's willingness to donate an organ while alive or after death. The responses were analyzed by using SAS software (SAS Institute). RESULTS: A total of 572 participants completed the survey. Overall, only 6.5% of surveyed students were unwilling to donate after death. The willingness to donate while alive to a family member was significantly higher than donating to a stranger (95.8% vs 71.2%, P < .0001). When merit points were added, the unwillingness to donate significantly decreased from 6.5% to 3.8%. However, this change was observed only when the merit points were given to a family member and not to self. When merit points were granted, unwillingness to provide a living donation to a stranger decreased from 28.8% to 16.4% (P < .0001). CONCLUSIONS: Merit points to first-degree family members improve students' expressed willingness to donate organs after death; however, self-merit points did not decrease the rate of "unwillingness to donate after death." When living donation is assessed, offering merit points appears to decrease the "unwillingness to donate to strangers." The adoption of a merit point system in the United States may increase the rates of organ donation.

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.

Gabapentin, Concomitant Prescription of Opioids, and Benzodiazepines among Kidney Transplant Recipients.

BACKGROUND: Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS: We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS: Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS: Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

International Practices on COVID-19 Vaccine Mandates for Transplant Candidates.

Background: The coronavirus disease 2019 (COVID-19) pandemic created unprecedented challenges for solid organ transplant centers worldwide. We sought to assess an international perspective on COVID-19 vaccine mandates and rationales for or against mandate policies. Methods: We administered an electronic survey to staff at transplant centers outside the United States (October 14, 2021-January 28, 2022) assessing the reasons cited by transplant centers for or against implementing a COVID-19 vaccine mandate. Each responding center was represented once in the analysis. Results: Respondents (N=90) represented 27 countries on five continents. Half (51%) of responding transplant center representatives reported implementing a COVID-19 vaccine mandate, 38% did not, and 12% were unsure. Staff at centers implementing a vaccine mandate cited efficacy of pretransplant vaccination versus post-transplant vaccination, importance for public health, and minimizing exposure of other patients as rationale for the mandate. Of centers with a mandate, the majority (81%) of the centers mandate vaccination regardless of prior SARS-CoV-2 infection status and regardless of prevaccination spike-protein antibody titer or other markers of prior infection. Only 27% of centers with a vaccine mandate for transplant candidates also extended a vaccine requirement to living donor candidates. Centers not implementing a vaccine mandate cited concerns for undue pressure on transplant candidates, insufficient evidence to support vaccine mandates, equity, and legal considerations. Conclusions: The approach to pretransplant COVID-19 vaccination mandate policies at international transplant centers is heterogeneous. International transplant centers with a vaccine mandate were more willing to extend vaccine requirements to candidates' support persons, cohabitants, and living donors. Broader stakeholder engagement to overcome vaccine hesitancy across the world is needed to increase the acceptance of pretransplant COVID-19 vaccination to protect the health of transplant patients.

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.

Costs in the Year Following Deceased Donor Kidney Transplantation: Relationships With Renal Function and Graft Failure.

Relationships between renal function and medical costs for deceased donor kidney transplant recipients are not fully quantified post-transplant. We describe these relationships with renal function measured by estimated glomerular filtration rate (eGFR) and graft failure. The United States Renal Data System identified adults receiving single-organ deceased donor kidneys 2012-2015. Inpatient, outpatient, other facility costs and eGFRs at discharge, 6 and 12 months were included. A time-history of costs was constructed for graft failures and monthly costs in the first year post-transplant were compared to those without failure. The cohort of 24,021 deceased donor recipients had a 2.4% graft failure rate in the first year. Total medical costs exhibit strong trends with eGFR. Recipients with 6-month eGFRs of 30-59 ml/min/1.73m2 have total costs 48% lower than those <30 ml/min/1.73m2. For recipients with graft failure monthly costs begin to rise 3-4 months prior to failure, with incremental costs of over $38,000 during the month of failure. Mean annual total incremental costs of graft failure are over $150,000. Total costs post-transplant are strongly correlated with eGFR. Graft failure in the first year is an expensive, months-long process. Further reductions in early graft failures could yield significant human and economic benefits.

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.

Survey of current transplant center practices regarding COVID-19 vaccine mandates in the United States.

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021-November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.

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.

Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age.

BACKGROUND: Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. METHODS: Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). RESULTS: Of 12 488, 28.3% recipients received ESW. The incidence rate for PTD was 13 per 100 person-y and lower among recipients who received ESW (11 per 100 person-y in ESW; 14 per 100 person-y in CSM). Overall, ESW was associated with lower risk of PTD compared with CSM (adjusted hazard ratio [aHR] = 0.720.790.86), but the risk differed by recipient age (P interaction = 0.09 for comparison between recipients aged 18-29 and those aged 30-54; P interaction = 0.01 for comparison between recipients aged 18-29 and those aged ≥55). ESW was associated with lower risk of PTD among recipients aged ≥55 (aHR = 0.620.710.81) and those aged 30-54 (aHR = 0.730.830.95), but not among recipients aged 18-29 (aHR = 0.811.181.72). Although recipients who received ESW had a higher risk of acute rejection across the age groups (adjusted odds ratio = 1.011.171.34), recipients with no PTD had a lower risk of mortality (aHR = 0.580.660.74). CONCLUSIONS: The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.