Transplantation最新文献

Background: Identification and treatment of latent tuberculosis infection (LTBI) mitigate the risk of tuberculosis (TB) reactivation after transplantation. TB reactivation is higher in those with indeterminate QuantiFERON (QFT) than those with negative results. Management of indeterminate QFT results in the pretransplant period remains unclear.

Methods: We conducted a retrospective study of solid organ transplant (SOT) recipients, 18 y and older, who were screened with QFT assay pretransplantation at Mayo Clinic between January 2010 and June 2023. We examined the frequency of indeterminate QFT results, results of repeat LTBI screening, treatment decisions, and rate of posttransplant TB infection.

Results: Of 13 008 patients screened for LTBI before SOT, 736 (6%) patients had indeterminate QFT results. Among these, 247 (34%) underwent a second LTBI screening test, and 39 (5%) received LTBI treatment. Among 247 patients with a repeat LTBI screening test, 185 (75%), 48 (19%), and 14 (6%) were tested by QFT, T-SPOT.TB, or TST, respectively. The repeat QFT remained indeterminate in 160 (86%) patients, whereas all T-SPOT.TB results were negative. Posttransplant TB infection occurred in 2 (0.3%) patients; neither had a second TB screening test pretransplant nor received LTBI treatment.

Conclusions: In SOT recipients with indeterminate QFT results at pretransplant evaluation, opting for T-SPOT.TB as a second test may be preferable over repeat QFT. TB infection after transplantation in patients with a pretransplant indeterminate QFT result was rare. Patient management and LTBI treatment in those with indeterminate QFT pretransplant should account for epidemiological risk factors, and shared decision-making is recommended.

Background: In recent years, changes to US organ allocation have aimed to improve equity and accessibility across regions. The Organ Procurement and Transplantation Network plans to adopt continuous liver distribution, prioritizing candidates based on a weighted composite allocation score (CAS) incorporating proximity, ABO types, medical urgency, and pediatric priority. The Liver Committee has requested research on CAS variations that account for geographical heterogenicity.

Methods: We describe a method for designing a geographically heterogeneous CAS with targeted broader sharing (CAS-TBS) to balance the highly variable geographic distributions of liver transplant listings and liver donations. CAS-TBS assigns each donor hospital to either broader sharing or nearby sharing, adjusting donor-candidate distance allocation points accordingly.

Results: We found that to reduce geographic disparity in the median Model for End-stage Liver Disease at transplant (MMaT), >75% of livers recovered in regions 2 and 10 should be distributed with broader sharing, whereas 95% of livers recovered in regions 5 and 1 should be distributed with nearby sharing. In a 3-y simulation of liver allocation, CAS-TBS decreased MMaT by 2.1 points in high-MMaT areas such as region 5 while increasing MMaT only by 0.65 points in low-MMaT areas such as region 3. CAS-TBS significantly decreased median transport distance from 202 to 167 nautical miles under acuity circles and decreased waitlist deaths.

Conclusions: Our CAS-TBS design methodology could be applied to design geographically heterogeneous allocation scores that reflect transplant community values and priorities within the continuous distribution project of the Organ Procurement and Transplantation Network. In our simulations, the incremental benefit of CAS-TBS over CAS was modest.

Background: HLA-DQ mismatch has been identified as a predictor of de novo donor-specific HLA antibody formation and antibody-mediated rejection. There are insufficient data to guide the incorporation of DQ mismatch into organ allocation decisions.

Methods: We used a retrospective longitudinal cohort of adult living donor kidney transplant recipients from 11 centers across the United States for whom high-resolution class II typing was available. HLA-DQαβ heterodimer allele mismatch was quantified for all donor-recipient pairs, and outcome data were obtained through linkage with the Scientific Registry of Transplant Recipients.

Results: We studied 3916 donor-recipient pairs. Recipient characteristics were notable for a median age of 51 (38-61) y, primarily unsensitized, with 74.5% of the cohort having 0% calculated panel-reactive antibody, and 60.4% with private insurance, for a median follow-up time of 5.86 y. We found that the HLA-DQαβ allele and HLA-DR antigen mismatch were each individually associated with an increased hazard of all-cause graft failure (adjusted hazard ratio [aHR] DQ = 1.03 1.14 1.28; aHR DR = 1.03 1.15 1.328), death-censored graft failure (aHR DQ =1.01 1.19 1.40; aHR DR = 0.099 1.18 1.39), and rejection. Having 2 HLA-DQαβ allele mismatches further increased the hazard of rejection even when controlling for HLA-DR mismatch (aHR 1.03 1.68 2.74).

Conclusions: HLA-DQαβ allele mismatch predicted allograft rejection even when controlling for HLA-DR antigen mismatch and were both independently associated with increased risk of graft failure or rejection in adult living kidney transplant recipients. Given the strong burden of disease arising from the HLA-DQ antibody formation, we suggest that HLA-DQαβ should be prioritized over HLA-DR in donor selection.

Background: Existing methods of comparing organ procurement organization (OPO) performance use administrative data to indirectly measure donation after circulatory death (DCD). The purpose of this study was to categorize and quantify reasons that potential DCD donors do not progress to donation to facilitate the direct measurement of OPO donor potential.

Methods: Records of all 18 685 potential organ donors referred to the organ procurement agency OneLegacy in 2021 and 2022 were reviewed, and reasons that cases did not proceed to donation were categorized and quantified. All hospital deaths were reviewed through tissue referrals and chart audits to assess whether potential organ donors were not referred.

Results: There were 8349 potential DCD donors. Of these, 5640 cases were ruled out for clinical reasons, and 1458 cases were ruled out for factors unique to DCD, such as ventilation, which was never withdrawn. Of the 1251 ruled in for the family approach to donation consent, there were ultimately 191 donors with organs transplanted.

Conclusions: OPO donor potential calculated from referral and hospital death record reviews is substantially lower than donor potential determined by administrative data, validating the need for direct measurement for regulatory purposes and performance improvement. For a usable direct measure of donor potential, DCD donor criteria must be codified, electronic donor records optimized, and audit processes developed.

Background: This study evaluates the clinical trends and impact of hepatitis C virus-positive (HCV+) donors on waitlist and posttransplant outcomes after heart transplantation.

Methods: The United Network for Organ Sharing registry was queried to identify adult waitlisted and transplanted patients from January 1, 2015, to December 31, 2022. In the waitlist analysis, the candidates were stratified into 2 cohorts based on whether they were willing to accept HCV+ donor offers. Waitlist outcomes included 1-y cumulative incidences of transplantation and death/delisting. In the posttransplant analysis, the recipients were stratified into 2 cohorts with and without HCV nucleic acid test (NAT)-positive donors. Outcomes included 1- and 4-y posttransplant survival. Propensity score-matching was performed. Risk adjustment was performed using multivariable Cox regression.

Results: During the study period, the number of centers using HCV NAT+ donors increased from 1 to 65 centers, along with the number of transplants. In the waitlist analysis, 26 648 waitlisted candidates were analyzed, and 4535 candidates (17%) were approved to accept HCV+ donors. Approval to accept HCV+ donors was associated with a higher likelihood of transplantation and a lower likelihood of death/delisting within 1 y of waitlisting. In the posttransplant analysis, 21 131 recipients were analyzed, and 997 recipients (4.7%) received HCV NAT+ hearts. The 1- and 4-y posttransplant survival were comparable between the recipients of HCV NAT+ and NAT- donors. Furthermore, the similar 1- and 4-y posttransplant survival persisted in the propensity score-matched comparison and multivariable Cox regression analysis.

Conclusions: Utilization of HCV+ donors is rising. Heart transplants using HCV+ donors are associated with improved waitlist and comparable posttransplant outcomes.

Background: Severe primary graft dysfunction (PGD) after lung transplantation (LTx) is a significant risk factor for the development of bronchiolitis obliterans syndrome (BOS). Recent data from our group demonstrated that small extracellular vesicles (sEVs) isolated from the plasma of LTx recipients with BOS have reduced levels of tumor suppressor gene liver kinase B1 (LKB1) and promote epithelial-to-mesenchymal transition (EMT) and fibrosis. Here, we hypothesized that early inflammatory responses associated with severe PGD (PGD2/3) can downregulate LKB1 levels in sEVs, predisposing to the development of chronic lung allograft dysfunction (CLAD).

Methods: sEVs were isolated from the plasma of human participants by Exosome Isolation Kit followed by 0.20-µm filtration and characterized by NanoSight and immunoblotting analysis. Lung self-antigens (K alpha 1 tubulin, Collagen V), LKB1, nuclear factor kappa B, and EMT markers in sEVs were compared by densitometry analysis between PGD2/3 and no-PGD participants. Neutrophil-derived factors and hypoxia/reperfusion effects on LKB1 levels and EMT were analyzed in vitro using quantitative real-time polymerase chain reaction and Western blotting.

Results: LKB1 was significantly downregulated in PGD2/3 sEVs compared with no-PGD sEVs. Within PGD2/3 participants, lower post-LTx LKB1 was associated with CLAD development. Hypoxia/reperfusion downregulates LKB1 and is associated with markers of EMT in vitro. Finally, lower LKB1 levels in PGD2/3 are associated with increased markers of EMT.

Conclusions: Our results suggest that in post-LTx recipients with PGD2/3, downregulation of LKB1 protein levels in sEVs is associated with increased EMT markers and may result in the development of CLAD. Our results also suggest that ischemia/reperfusion injury during LTx may promote CLAD through the early downregulation of LKB1.