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.

Indications, Techniques, and Barriers for Pancreas Transplant Biopsy: A Consensus Perspective From a Survey of US Centers.

BACKGROUND: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described. METHODS: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies. RESULTS: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist's or biopsy performer's comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically. CONCLUSIONS: This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted.

The 50% effective dose of hydromorphone and morphine for epidural analgesia in the hemorrhoidectomy: a double-blind, sequential dose-finding study.

BACKGROUND: Although previous studies have showed that epidural morphine can be used as a complement to local anesthetics for analgesia after postcesarean delivery under spinal anesthesia, there is little known about the analgesic dosage of epidural morphine and hydromorphone for hemorrhoidectomy. Therefore, we conducted this study to examine the potency ratio of hydromorphone to epidural morphine as well as effective analgesic dose for 50% patients (ED50) undergoing elective hemorrhoidectomy. METHODS: 80 patients under elective hemorrhoidectomy with combined spinal and epidural anesthesia(CSEA) in department of anesthesia, Dongguan Tungwah hospital. To assess the ED50, patients were treated with epidural morphine or epidural hydromorphone randomly using a biased coin method-determined dose with a sequential allocation procedure. Following surgery, standardized multimodal analgesia was administered to all patients. A pain response score of ≤ 3 (on a scale of 0-10) was determined to be the effective dose after 24 h following CSEA. The ED50 in both groups were determined using the probit regression and isotonic regression method. We also measured pain intensity by patient interview using a 10 point verbal numeric rating scale prospectively at 6, 12 and 24 h after CSEA, and adverse effects were also noted. RESULTS: The ED50 was 0.350 mg (95% CI, 0.259-0.376 mg) in hydromorphone group and 1.129 mg (95% CI, 0.903-1.187 mg) in morphine group, respectively, estimated by isotonic regression method. Regression analysis with the probit, the ED50 of epidural hydromorphone was 0.366 mg (95% CI, 0.276-0.388 mg) and epidural morphine was 1.138 mg (95% CI, 0.910-1.201 mg). Exploratory findings showed that there was no difference between the most frequent dosages of epidural hydromorphone or epidural morphine in the occurrence of nausea, vomiting and pruritus. When administered with epidural opioids at ED50 doses or higher, 97.5% (39/40) of epidural morphine patients and 97.5% (39/40) epidural hydromorphone of patients were satisfied with their analgesia. CONCLUSION: Effective hemorrhoidectomy analgesia requires a 3:1 ratio of epidural morphine to epidural hydromorphone. Both drugs provide excellent patient satisfaction.

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.

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.

Factors enabling transplant program participation in the Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective: A national survey.

BACKGROUND: The Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective (LDC), the first effort to create a lifetime registry for living donor candidates in the United States, requires transplant programs to register donor candidates while the SRTR conducts follow-up. METHODS: To better understand facilitators and barriers to program participation, we conducted a brief electronic survey of U.S. transplant program staff from October 26, 2021 to December 17, 2021. RESULTS: We received 132 responses, with at least one response from 87 living donor programs (46 kidney programs, 33 kidney and liver programs, and eight liver programs alone). We found 86% of program representatives strongly agreed or agreed that funding adequate to cover the cost of data collection would facilitate LDC participation, 92% agreed or strongly agreed with importance of electronic data submission options, and 74% reported that elimination of requirements to submit duplicative pre-operative information to the Organ Procurement and Transplantation Network (OPTN) would be helpful. Other potentially enabling factors include reduction in duration of OPTN postdonation follow-up requirements, ease-of-use, protection from data use for regulation, adequate data security, and equity in data access. CONCLUSION: This survey identifies potential targets to strengthen participation in the effort to create a national living donor registry in the United States. Collaboration and investment to overcome barriers to LDC participation among transplant programs are vital to generate long-term data on living donation for donor candidates, donors, and patients in need of transplant.

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.

Managing the Costs of Routine Follow-up Care After Living Kidney Donation: a Review and Survey of Contemporary Experience, Practices, and Challenges.

Purpose of Review: While living organ donor follow-up is mandated for 2 years in the USA, formal guidance on recovering associated costs of follow-up care is lacking. In this review, we discuss current billing practices of transplant programs for living kidney donor follow-up, and propose future directions for managing follow-up costs and supporting cost neutrality in donor care. Recent Findings: Living donors may incur costs and financial risks in the donation process, including travel, lost time from work, and dependent care. In addition, adherence to the Organ Procurement and Transplantation Network (OPTN) mandate for US transplant programs to submit 6-, 12-, and 24-month postdonation follow-up data to the national registry may incur out-of-pocket medical costs for donors. Notably, the Centers for Medicare and Medicaid Services (CMS) has explicitly disallowed transplant programs to bill routine, mandated follow-up costs to the organ acquisition cost center or to the recipient's Medicare insurance. We conducted a survey of transplant staff in the USA (distributed October 22, 2020-March 15, 2021), which identified that the mechanisms for recovering or covering the costs of mandated routine postdonation follow-up at responding programs commonly include billing recipients' private insurance (40%), while 41% bill recipients' Medicare insurance. Many programs reported utilizing institutional allowancing (up to 50%), and some programs billed the organ acquisition cost center (25%). A small percentage (11%) reported billing donors or donors' insurance. Summary: To maintain a high level of adherence to living donor follow-up without financially burdening donors, up-to-date resources are needed on handling routine donor follow-up costs in ways that are policy-compliant and effective for donors and programs. Development of a government-supported national living donor follow-up registry like the Living Donor Collective may provide solutions for aspects of postdonation follow-up, but requires transplant program commitment to register donors and donor candidates as well as donor engagement with follow-up outreach contacts after donation. Supplementary Information: The online version contains supplementary material available at 10.1007/s40472-022-00379-w.

Relationship Between Hypertension and Basilar Atherosclerosis in Chinese Han Population: A High-Resolution Magnetic Resonance Imaging Study.

Objective: To investigate the relationship between hypertension and basilar atherosclerosis evaluated by high-resolution magnetic resonance imaging (HR-MRI) in the Chinese Han population. Methods: High resolution-MRI vessel wall imaging was performed in selected 193 patients for various indications. Multivariable logistic regression models based on odds ratio (OR) with their associated 95% confidence interval (CI) were used to assess the relationship between hypertension and basilar artery (BA) plaque, moderate or severe stenosis of BA plaque, and vulnerable plaque. A linear regression model was used to assess the relationship between hypertension and BA plaque numbers. Results: Patients with hypertension had a higher proportion of BA plaque and vulnerable plaque as well as more number of enhancements of BA plaque and serious plaque compared with normotensive patients (all values of p < 0.05). Multivariable logistic regression analysis indicated that patients with hypertension had an increased risk for and more number of enhancements of BA plaque (adjusted-OR: 4.32, 95% CI 1.89-9.88, p < 0.001; adjusted-ß: 0.55, 95% CI 0.14-0.96, p = 0.009, respectively) and had a higher proportion of moderate or severe stenosis of BA plaque and vulnerable plaque (adjusted-OR: 3.08, 95% CI 0.77-12.32, p = 0.111; adjusted-OR: 4.52, 95% CI 1.50-13.64, p = 0.007, respectively) compared with the normotensive group. Moreover, there was a saturation effect of age on the prevalence of BA plaque and vulnerable plaque. Conclusion: Hypertension was the independent risk factor of BA plaque and vulnerable plaque assessed by HR-MRI in the Chinese Han population.

Effect of high-throughput screening of circRNA01724 on a rat model of myocardial ischemia ventricular arrhythmia.

Background: It is considered that circRNA can participate in regulating the occurrence and effects of ventricular arrhythmia (VA) through competing endogenous RNA (ceRNA) mechanism, regulating pre-mRNA and regulating parental gene expression. Therefore, we used animal modeling and high-throughput differential screening to screen out circRNA related to VA and study its possible mechanism of action on VA. Methods: The rat model of myocardial ischemia VA was established. High-throughput screening of the differentiated circRNA was conducted and verified by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. Lv-circRNA01724 lentivirus was constructed using molecular biology. Primary isolation of the rat cardiomyocytes, hypoxia modeling, Lv-circRNA01724 transfection, mode of action verification, and dual luciferase detection of circRNA01724 and miR-323-5p was performed. Results: Through qRT-PCR verification of circRNA01724, circRNA02230, circRNA02088, miR-323-5p, miR-330-5p, and miR-324-3p expressions, circRNA01724 was selected as the research object. Detection by Western blot showed significantly lower Cx43, ZO-1, and α-catenin expressions in rat myocardial tissue in the model group compared with the control group at 1, 7, 14, and 28 days old. On identification of the isolated primary rat cardiomyocytes by immunofluorescence, the α-SMA characteristic protein expression indicated that the isolation was successful. Verification of rat cardiomyocytes transfected with Lv-circRNA01724 suggested overexpression in cells. The miR-323-5p was also highly expressed in the rat cardiomyocyte hypoxia model following Lv-circRNA01724 transfection. Detection by flow cytometry showed that modeling of the transfected Lv-circRNA01724 had a significant increased apoptotic rate. Detection by Western blot showed that modeling of the transfected Lv-circRNA01724 cells had significantly decreased Cx43, ZO-1, and α-catenin compared with the model group. Conclusions: High-throughput screening of circRNA01724 can promote the apoptosis of hypoxic cardiomyocytes, which is related to the rat model of myocardial ischemia VA and may be a potential target for the treatment of VA.

Long noncoding RNA LINC01296 regulates the cell proliferation, migration and invasion in neuroblastoma.

Neuroblastoma (NB) is a childhood cancer that often occurs in the sympathetic nervous system. Previous reports showed that long non-coding RNAs (lncRNAs) could affect the progress of NB, but the mechanism is still indistinct. In this study, we unfolded the roles of LINC01296 in NB tissues and cells. The level of LINC01296, microRNA-584-5p (miR-584-5p), miR-34a-5p and mRNA of tripartite motif-containing 59 (TRIM59) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in NB tissues. The capacities of NB cells were validated by MTT assay, Edu assay, transwell assay and flow cytometry analysis. The interplay between miR-584-5p/miR-34a-5p and LINC01296 or TRIM59 were detected by dual-luciferase reporter assay. Finally, the in vivo experiment was implemented to verify the effect of LINC01296 in vivo. The level of LINC01296 and TRIM59 were increased, whereas miR-584-5p and miR-34a-5p levels were reduced in NB tissues in contrast to that in normal tissues. For functional analysis, LINC01296 deficiency inhibited the cell vitality, cell proliferation, migration and invasion in NB cells, whereas promoted cell apoptosis. Moreover, miR-584-5p and miR-34a-5p were validated to act as a tumor repressive effect in NB cells by restraining TRIM59. The results also showed that LINC01296 could regulate the development of NB. In mechanism, LINC01296 acted as a miR-584-5p and miR-34a-5p sponge to modulate TRIM59 expression. In addition, LINC01296 knockdown also attenuated tumor growth in vivo. LINC01296 promotes the progression of NB by increasing TRIM59 expression via regulating miR-584-5p and miR-34a-5p, which also offered an underlying targeted therapy for NB treatment.

Extracellular vesicles derived from HBMSCs improved myocardial infarction through inhibiting zinc finger antisense 1 and activating Akt/Nrf2/HO-1 pathway.

Myocardial infarction (MI) is believed to be one of the most common cardiovascular diseases, and it is seriously threatening the health of people in the world. The extracellular vesicles (EVs) isolated from mesenchymal stem cells and zinc finger antisense 1 (ZFAS1) have been believed to be involved in the regulation of MI, but the mechanism has not been fully clarified. Left anterior descending artery ligation was used to establish MI animal model, hypoxia treatment was applied to establish MI cell model. CCK8, transwell, and wound healing methods were applied to measure cell proliferation, invasion, and migration. Overexpression of ZFAS1 was established via transfecting pcDNA-ZFAS1. Overexpression of ZFAS1 significantly reversed the influence of EVs on cell migration, invasion, and apoptosis. Similar effect of EVs and ZFAS1 on morphological changes of MI rat heart tissues were also observed. The activation of Akt/Nrf2/HO-1 pathway by EVs was remarkably suppressed by pcDNA-ZFAS1. Inhibitor of Akt/Nrf2/HO-1 pathway remarkably reversed the impact of EVs on the cell viability. EVs might improve MI through inhibiting ZFAS1 and promoting Akt/Nrf2/HO-1 pathway. This study might provide a new thought for the prevention and treatment of MI damage through regulating ZFAS1 or Akt/Nrf2/HO-1 pathway.

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.

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.

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.

Clinical Correlates and Outcomes of Dual Basiliximab and Antithymocyte Globulin Induction in Kidney Transplant Recipients: A National Study.

The unplanned use of dual induction therapy with interleukin-2 receptor-blocking antibodies (IL2rAb) and antithymocyte globulin (ATG) may portend adverse outcomes. Methods: We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 y, according to induction therapy type, was assessed using multivariate Cox regression analysis (adjusted hazard ratio with 95% upper and lower confidence limits [LCLaHRUCL]). Results: Of the 157 351 recipients included in the study, 67% were treated with ATG alone, 29% were treated with IL2rAb alone, and 5% were treated with both. Compared with IL2rAb alone, the strongest correlates of dual induction included Black race, calculated panel reactive antibody ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with ATG alone, dual induction was associated with an increased 5-y risk of death (aHR 1.071.151.23; P < 0.0001), death-censored graft failure (aHR 1.051.131.22; P < 0.05), and all-cause graft failure (aHR 1.061.121.18; P < 0.0001). Conclusions: Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.

Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis.

BACKGROUND: Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group. METHODS: National data for US Medicare-insured adult kidney recipients (N = 67 362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure, and mortality using multivariable regression analysis in younger (18-64 y) and older (>65 y) adults. RESULTS: The use of antithymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% versus 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% versus 20.1%) and mammalian target of rapamycin inhibitor (mTORi)-based (6.7% versus 7.7%) treatments. Conversely, older patients were more likely to receive interleukin (IL)-2-receptor antibody (IL2rAb) + triple maintenance (21.1% versus 14.7%), IL2rAb + steroid avoidance (4.1% versus 1.8%), and cyclosporine-based (8.3% versus 6.6%) immunosuppression. Compared with older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio [aOR], 0.440.520.61) and IL2rAb + steroid avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death-censored graft failure when managed with Tac + antimetabolite avoidance (adjusted hazard [aHR], 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients. CONCLUSIONS: Lower-intensity immunosuppression regimens (eg, steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.

Financial Evaluation of Kidney Transplant With Hepatitis C Viremic Donors to Uninfected Recipients.

Kidney transplantation with hepatitis C viremic (dHCV+) donors appears safe for recipients without HCV when accompanied by direct acting antiviral (DAA) treatment. However, US programs have been reluctant to embrace this approach due to concern about insurance coverage. While the cost of DAA treatment is currently offset by the reduction in waiting time, increased competition for dHCV+ organs may reduce this advantage. This analysis sought to demonstrate the financial benefit of dHCV+ transplant for third-party health insurers to expand coverage availability. METHODS: An economic analysis was developed using a Markov model for 2 decisions: first, to accept a dHCV+ organ versus wait for a dHCV uninfected organ; or second, accept a high kidney donor profile index (KDPI) (>85) organ versus wait for a better quality dHCV+ organ. The analysis used Medicare payments, historical survival data, cost report data, and an estimated cost of DAA of $29 874. RESULTS: In the first analysis, using dHCV+ kidneys reduced the cost of end-stage kidney disease care if the wait for a dHCV uninfected organ exceeded 11.5 months. The financial breakeven point differed according to the cost of DAA treatment. In the second analysis, declining a high-KDPI organ in favor of a waiting dHCV+ organ was marginally clinically beneficial if waiting times were <12 months but not cost effective. CONCLUSIONS: dHCV+ transplant appears to be economically and clinically advantageous compared with waiting for dHCV-uninfected transplant but should not replace high-KDPI transplant when appropriate. Despite the high cost of DAA therapy, health insurers benefit financially from dHCV+ transplant within 1 year.