Epidemiology, risk factors, and outcomes of lung retransplantation: An analysis of the International Society for Heart and Lung Transplantation Thoracic Transplant Registry.

BACKGROUND: Lung retransplantation is a complex surgical decision that represents the only potential treatment option for recipients suffering from lung allograft failure. We sought to describe the modern landscape of lung retransplantation and to compare the relative importance of selected clinical, donor, and recipient factors on mortality in the year following lung retransplantation. METHODS: We conducted a retrospective cohort study of first-time adult recipients of deceased donor lung retransplants reported to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry from May 2005 through June 2017. In addition to describing the characteristics of lung retransplant recipients, we examined 1 year survival overall, and by initial transplant-retransplant procedure type, recipient age, retransplant indication, and time-to-lung retransplantation (i.e., inter-transplant interval). We used the Somers' Dxy rank correlation statistic for censored data to assess the relative importance of several potential prognostic risk factors for mortality in the year following lung retransplantation. RESULTS: Our cohort included 1,597 lung retransplant recipients. 2005 was the first year with more than 100 retransplants, and since 2007, 138 to 188 retransplants (approximately 4%-6% of all transplants) were reported annually to the ISHLT Registry. The median inter-transplant interval was 3.4 years (interquartile range: 1.6-6.2 years). Forty-three percent of the cohort had an obliterative bronchiolitis retransplant indication, whereas 17% had primary graft failure. One-third (32%) were retransplanted within 2 years of their primary transplant, and 64% received a double lung transplant both times, whereas 36% received consecutive single lung transplants. Six-month and 1 year survival (82% and 76%) were higher for double-double lung retransplant recipients than for single-single recipients (76% and 69%). The 3 strongest prognostic factors for 1 year mortality were the inter-transplant interval (decreasing hazard with longer intervals), donor age (increasing hazard with older age), and need for mechanical ventilation preceding lung retransplantation. CONCLUSIONS: Retransplants comprise approximately 5% of annual lung transplants worldwide. The factor most strongly associated with 1 year mortality in this population was the duration of time since the primary lung transplant, with a persistent reduction in risk as more time elapses.

Cytomegalovirus Donor Seropositivity Negatively Affects Survival After Heart Transplantation.

BACKGROUND: Prior studies have shown that cytomegalovirus (CMV) infection is a risk factor for the development of cardiac allograft vasculopathy (CAV) and is associated with reduced long-term survival after heart transplantation (HTx). The aim of this International Society for Heart and Lung Transplantation Transplant Registry study was to compare posttransplant survival in different CMV donor:recipient serologic combinations. METHODS: We performed a retrospective cohort study, using the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, on 15 885 adult primary heart transplant recipients with known CMV serologic status between July 2004 and June 2014. Posttransplant survival and risk of developing CAV were compared across 4 groups: CMV-seronegative recipients (R-) receiving CMV-positive grafts (D+), intermediate-risk patients (D+R+ and D-R+), and low-risk patients (D-R-). RESULTS: Baseline characteristics (donor/recipient age, body mass index, recipient serum creatinine, blood group, donor cause of death, recipient diagnosis, and ischemic time) were mostly balanced between the groups. Kaplan-Meier survival analyses over a follow-up of 10 y revealed significantly worse survival for both D+ groups as compared to the CMV low-risk group (D+R+: 56.61% [95% confidence interval, 53.94-59.41] versus D-R-: 63.09% [59.74-66.64] P < 0.01 and D+R-: 57.69% [56.03-59.39] versus D-R-; P < 0.001), whereas recipient seropositivity alone was not associated with reduced survival (D-R+ versus D-R-P = 0.178). The risk of developing CAV after HTx was not significantly increased in D+ as compared to D- groups. CONCLUSIONS: In a large contemporary cohort, CMV status at the time of HTx was not associated with CAV development. However, there was a significant association between donor CMV seropositivity and reduced short- and long-term survival after HTx. Approaches to mitigate the impact of CMV on posttransplant survival are needed.

The Advantage of Multiple Listing Continues in the Kidney Allocation System Era.

BACKGROUND: Transplant candidates can be listed at multiple transplant centers to increase the probability of receiving an organ. We evaluated the association between multilisting (ML) status and access to a deceased donor kidney transplant (DDKT) to determine if ML provides a long-term advantage regarding wait-list mortality and recipient outcomes. MATERIALS AND METHODS: Candidates between January 2010 and October 2017 were identified as either singly or multiply listed using Organ Procurement and Transplantation Network data and cohorts before and after implementation of the Kidney Allocation System (KAS). Cross-sectional logistic regression was used to assess relationships between candidate factors and ML prevalence (5.4%). RESULTS: Factors associated with ML pre-KAS included having blood type B (reference, type O; odds ratio [OR], 1.20; P < .001), having private insurance (OR, 1.5; P < .001), wait time (OR, 1.28; P < .001), and increasing calculated panel-reactive antibody (cPRA) (reference, cPRA 0-100; OR for cPRA 80-98, 2.83; OR for cPRA 99, 3.47; OR for cPRA 100, 5.18; P < .001). Transplant rates were double for multilisted vs singly listed recipients (adjusted hazard ratio [aHR], 2.16; P < .001). Extra-donor service area ML candidates received transplants 2.5 years quicker than single-listing (SL) candidates, conferring a 42% wait-list advantage. Recipient death (aHR, 0.94; P = .122) and graft failure (aHR, 0.91; P = .006) rates were also lower for ML recipients. CONCLUSIONS: In the KAS era, ML continues to increase the likelihood of receiving a DDKT and lower the incidence of wait-list mortality, and it confers a survival advantages over SL.

Kidney allograft rejection: Diagnosis and treatment practices in USA- A UNOS survey.

We studied diverse rejection management strategies across centers by conducting a UNOS survey of kidney transplant program directors in 2017. There were 104 total responses from 235 kidney transplant programs representing 88 unique transplant programs (response rate 37%). Information was collected on center-specific management practices. Pertinent center-specific data were obtained from the OPTN database. Of the respondents, 33% were considered large centers (>100 transplants/year). Thymoglobulin was the most commonly used induction agent at 84%, 72% responders do rapid steroid withdrawal, and mycophenolic acid (MPA) is the major antimetabolite (100%). For diagnosing TCMR, 100% used indication biopsy, 28% used protocol biopsy, 2% used serum biomarkers, and none used urine cytokines. For ABMR, 99% used indication biopsy, 34% used protocol biopsy, 72% used DSA, 21% used C1q positive DSA, and none used gene profiling (ENDATS). The treatment of subclinical and clinical TCMR included iv/PO steroids. PP/IVIG were the commonest treatments for ABMR. The use of rituximab, bortezomib, and eculizumab increased from C4D-ABMR to recurrent ABMR. There are diverse management practices for diagnosing and treating rejection. An effort to harmonize these diverse practices for management of TCMR and ABMR will give an opportunity to pool data for evaluating clinical outcomes.

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (-90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (-45%), and other organs saw similar decreases: lung (-70%), heart (-43%), and liver (-37%). Deceased donors recovered dropped from 260 to 163 (-45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (-67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

Safety and Efficacy of a Steroid Avoidance Immunosuppression Regimen in Renal Transplant Patients With De Novo or Preformed Donor-Specific Antibodies: A Single-Center Study.

Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.

Increase in Alcoholic Hepatitis as an Etiology for Liver Transplantation in the United States: A 2004-2018 Analysis.

BACKGROUND: Changing opinions on the alcohol abstinence requirement have led to increased liver transplantation (LT) for alcoholic hepatitis (AH). We aimed to determine the trend in LT for AH in the United States and overall and graft survival rates. METHODS: Adult liver-alone and liver-kidney registrations added to the Organ Procurement and Transplantation Network waiting list between 2004 and 2018 were divided into 3 periods (2004-2009, 2010-2013, 2014-2018). Kaplan-Meier survival models illustrated patient and graft survival. RESULTS: Between 2004 and 2018, 529 AH patients were registered for and 254 received LT. By periods, 116, 73, and 340 patients were registered for and 49, 17, and 188 patients received LT, respectively, indicating a increase in LT for AH from 2014 to 2018. Yearly registrants from 2014 to 2018 were 32, 47, 51, 70, and 140, and recipients were 16, 24, 24, 38, and 88, respectively, indicating increases of 338% and 450% in registrants and recipients, respectively, since 2014. AH patients had the highest 1- and 3-year posttransplant survival (93.2% and 87.3%, respectively) and graft survival (90.4% and 84.8%, respectively) comparing to other LT recipients. CONCLUSIONS: LT for AH in the United States is at an all-time high with an increased overall patient and graft survival.

Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation.

Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.

Post-transplant outcome in patients bridged to transplant with temporary mechanical circulatory support devices.

BACKGROUND: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS. METHODS: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes. RESULTS: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time. CONCLUSIONS: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant.

Increasing Trends in Transplantation of HCV-Positive Livers Into Uninfected Recipients.

The introduction of direct-acting antiviral (DAA) agents and the opioid epidemic have resulted in an increased interest in liver transplantation (LT) of organs from donors with hepatitis C virus (HCV)-related viremia.1 In March of 2015, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) implemented a policy to perform HCV nucleic acid testing (NAT) in all HCV-seropositive donors. An open-label, single-center experience with 10 patients using a multistep informed consent reported successful transplantation of HCV-seropositive viremic (HCV-V) kidneys into HCV-seronegative recipients.2 Subsequently, a case was reported in which an HCV-V liver was transplanted into a HCV-seronegative recipient.3 In collaboration with OPTN/UNOS, we identified cases in which HCV-V deceased donor livers were transplanted into HCV-seronegative recipients.

Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era.

In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.