Progress in Transplantation最新文献

Introduction: Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited.

Project aim: The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation.

Design: This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N  =  505) during the same period.

Results: Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P  =  .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P  =  .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P  =  .001). Early allograft dysfunction was common (54.1% vs 52.5%, P  =  .75) and did not impact hospital length of stay (median 5 vs 6 days, P  =  .89). There were no differences in biliary complications (P  =  .11). There were no differences in patient (P  =  .88) or graft survival (P  =  .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers.

Conclusion: Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.

Introduction: Recovery of donated organs at organ procurement organization (OPO)-based recovery facilities has been proposed to improve organ donation outcomes, but few data exist to characterize differences between facilities and acute-care hospitals.

Research question: To compare donation outcomes between organ donors that underwent recovery procedures in OPO-based recovery facilities and hospitals.

Design: Retrospective study of Organ Procurement and Transplantation Network data. From a population-based sample of deceased donors after brain death April 2017 to June 2021, donation outcomes were examined in 10 OPO regions with organ recovery facilities. Primary exposure was organ recovery procedure in an OPO-based organ recovery. Primary outcome was the number of organs transplanted per donor. Multivariable regression models were used to adjust for donor characteristics and managing OPO.

Results: Among 5010 cohort donors, 2590 (51.7%) underwent recovery procedures in an OPO-based facility. Donors in facilities differed from those in hospitals, including recovery year, mechanisms of death, and some comorbid diseases. Donors in OPO-based facilities had higher total numbers of organs transplanted per donor (mean 3.5 [SD1.8] vs 3.3 [SD1.8]; adjusted mean difference 0.27, 95% confidence interval 0.18-0.36). Organ recovery at an OPO-based facility was also associated with more lungs, livers, and pancreases transplanted.

Conclusion: Organ recovery procedures at OPO-based facilities were associated with more organs transplanted per donor than in hospitals. Increasing access to OPO-based organ recovery facilities may improve rates of organ transplantation from deceased organ donors, although further data are needed on other important donor management quality metrics.

Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.

Introduction: Kidney transplant graft function depends on optimised haemodynamics. However, high fluid volumes risk hypervolaemic complications. The Edwards Lifesciences ClearSight™ device permits fluid titration through markers of preload and beat-to-beat blood pressure monitoring. We evaluated the implementation of a novel goal-directed haemodynamic therapy protocol to determine whether patient outcomes had improved. Design: A retrospective evaluation of standard care versus goal-directed haemodynamic therapy in adults undergoing kidney transplantation was performed in a single centre between April 2016 and October 2019. Twenty-eight standard-of-care patients received intraoperative fixed-rate infusion and 28 patients received goal-directed haemodynamic therapy. The primary outcome was volume of fluid administered intraoperatively. Secondary outcomes included blood product and vasoactive drug exposure, graft and recipient outcomes. Results: Intraoperative fluid administered was significantly reduced in the goal-directed haemodynamic therapy cohort (4325 vs 2751 ml, P < .001). Exposure to vasopressor (67.9% vs 42.9%, P = .060) and blood products (17.9% vs 3.6%, P = .101) was unchanged. Immediate graft function (82.1% vs 75.0%, P = .515), dialysis requirement (14.3% vs 21.4%, P = .729) and creatinine changes post-operatively were unchanged. In the goal-directed haemodynamic therapy cohort, 1 patient had pulmonary oedema (3.6%) versus 21.4% in the standard cohort. Patients in the goal-directed haemodynamic therapy group were more likely to mobilise within 48 hours of surgery (number needed to treat = 3.5, P = .012). Conclusions: Protocolised goal-directed haemodynamic therapy in kidney transplantation was safe and may improve patient, graft, and surgical outcomes. Clinical trials assessing goal-directed approaches are needed.

Introduction: In Australia and New Zealand, liver allocation is needs based (based on model for end-stage liver disease score). An alternative allocation system is a transplant benefit-based model. Transplant benefit is quantified by complex waitlist and transplant survival prediction models. Research Questions: To validate the UK transplant benefit score in an Australia and New Zealand population. Design: This study analyzed data on listings and transplants for chronic liver disease between 2009 and 2018, using the Australia and New Zealand Liver and Intestinal Transplant Registry. Excluded were variant syndromes, hepatocellular cancer, urgent listings, pediatric, living donor, and multi-organ listings and transplants. UK transplant benefit waitlist and transplant benefit score were calculated for listings and transplants, respectively. Outcomes were time to waitlist death and time to transplant failure. Calibration and discrimination were assessed with Kaplan-Meier analysis and C-statistics. Results: There were differences in the UK and Australia and New Zealand listing, transplant, and donor populations including older recipient age, higher recipient and donor body mass index, and higher incidence of hepatitis C in the Australia and New Zealand population. Waitlist scores were calculated for 2241 patients and transplant scores were calculated for 1755 patients. The waitlist model C-statistic at 5 years was 0.70 and the transplant model C-statistic was 0.56, with poor calibration of both models. Conclusion: The UK transplant benefit score model performed poorly, suggesting that UK benefit-based allocation would not improve overall outcomes in Australia and New Zealand. Generalizability of survival prediction models was limited by differences in transplant populations and practices.

Introduction: Kidney transplantation is associated with increased risk of bone fracture. Current literature reports widely variable fracture burden and contains limited data on risk factors for recurrent fractures. Methods: The incidence of all and major osteoporotic fractures (hip, forearm, thoracolumbar, and proximal humerus) were assessed. The risk factors for first and recurrent fractures among 1285 Canadian kidney transplant recipients transplanted between January 1, 2004, and December 31, 2013 were also identified. Results: The 10-year cumulative incidence of all fractures and major osteoporotic fractures in this population was 27.1% (95% CI: 22.5, 32.4) and 17.8% (95% CI: 13.4, 23.5), respectively. On multivariable analysis, female sex (HR = 1.64 [95% CI: 1.20, 2.26]), history of fracture (HR = 1.54 [95% CI: 1.12, 2.11]), and pretransplant diabetes (HR = 1.85 [95% CI: 1.29, 2.65]) were recipient factors found to increase the risk for any first fracture posttransplant. These risk factors persist in analysis with the time origin 3-months posttransplant, where transplant age (HR = 1.01 [95% CI: 1.00, 1.03]) and increased time on pretransplant dialysis (HR = 1.06 [95% CI: 1.00, 1.12]) also emerge as risk factors for first fracture. On multivariable shared frailty model analysis, increased risk of recurrent fractures was associated with recipient female sex (HR = 1.74 [95% CI: 1.21, 2.51]) and history of diabetes (HR = 1.76 [95% CI: 1.17, 2.66]). Discussion: The results suggested that some risk factors for first fracture may not inform risk of recurrent fractures. As such, fracture risk should be assessed accordingly to optimize long-term care and implement preventive measures.

Introduction: Few studies have compared within-patient variability measures of tacrolimus trough levels by formulation and assessed within-patient variability on outcomes of kidney transplant recipients.

Research questions: (1) To compare within-patient variability of trough levels when converting from twice-daily to once-daily tacrolimus using standard deviation, coefficient of variation, and intrapatient variability percent. (2) To use the 3 measures of variability to examine the relationship between tacrolimus once-daily within-patient variability and total graft failure (i.e., return to chronic dialysis, pre-emptive retransplant, death with graft function).

Design: In this observational cohort study, within-patient variability of trough levels pre- and post-conversion from twice-daily to once-daily tacrolimus were compared using Wilcoxon matched-pairs signed-rank test. Graft outcomes were analyzed using Kaplan-Meier curves and multivariable Cox proportional hazards models.

Results: In 463 patients, within-patient variability differences pre- and post-conversion of median standard deviation, coefficient of variation, and intrapatient variability percent were -0.16 (P = 0.09), -0.01 (P = 0.52), and -1.41 (P = 0.32), respectively. Post-conversion, every 1 unit increase in within-patient variability standard deviation and intrapatient variability percent and every 0.1 unit increase in the coefficient of variation was associated with an increased hazard ratio [1.19 (P = 0.004), 1.02 (P = 0.030), 1.13 (P = 0.001), respectively] of total graft failure. Post-conversion, within-patient variability above cohort medians using standard deviation and coefficient of variation had a significantly higher risk of total graft failure.

Discussion: Under a program-wide conversion, no significant difference was observed in within-patient variability post-conversion from twice-daily to once-daily tacrolimus using the three measures of variability. High within-patient variability was associated with adverse transplant outcomes post-conversion.

Introduction: Community-based participatory research and animated video offer promising approaches to attenuate disparities in access to kidney transplant information. Project Aims: We refined an evidence-based animated video curriculum (Kidney Transplant and Donation Information Made Easy) designed for diverse individuals, that is currently being trialed to advance kidney transplant access among referred patients at a single transplant center, to further accommodate information needs in earlier stages of the path to transplant (pre-referral) and to enhance fit for Black and Hispanic people. Design: We describe formation of an academic-community partnership and the application of qualitative research methods and partnership discussions to refine the Kidney Transplant and Donation Information Made Easy videos. A simple content analysis was undertaken of intervention refinement transcriptions, minutes, and meeting notes. Results: We formed a community steering committee and advisory board of local members predominantly of minoritized race or ethnicity. Full engagement with community members is evident in the program's adaptation process. Essential refinement elements were adaptation of 17 original videos and iterative development of 8 new videos with the community, conducting parallel cognitive interviews of an expanded sample of stakeholders, maintaining the theoretical grounding of Elaboration Theory, communication/multimedia learning best practices, and self-efficacy framework, and doing Spanish-language translation. Conclusions: Applying community-based participatory research principles and qualitative methods, we produced a culturally grounded adaptation of the Kidney Transplant and Donation Information Made Easy videos that provides information about kidney transplantation from primary care to transplantation. This approach is likely to strengthen our community partnership and eventual community acceptance of the intervention during the implementation phase. Challenges were achieving consensus and adding Spanish-language translation.