Transplantation Direct最新文献

Background: Donor-derived cell-free DNA (dd-cfDNA) is an emerging biomarker of kidney allograft injury, mainly investigated in the context of rejection. However, the dd-cfDNA dynamics in other graft pathologies merit further investigation.

Methods: In this single-center observational study, we prospectively collected dd-cfDNA at indication biopsies. To evaluate the association between dd-cfDNA and different histological patterns, we correlated absolute and relative dd-cfDNA (thresholds of 50 copies/mL and 0.5%, respectively) with the Banff 2022 lesion scores and the assigned diagnoses.

Results: We examined 151 dd-cfDNA paired biopsies in 131 kidney transplant recipients and found significantly higher absolute dd-cfDNA levels in antibody-mediated rejection (n, median, IQR: 45, 63 copies/mL, 42-89), microvascular inflammation (MVI) without donor-specific antibodies or C4d-deposition (6, 102 copies/mL, 61-134), mixed rejection (8, 140 copies/mL, 77-171), and BK virus-associated nephropathy (6, 213 copies/mL, 83-298) compared with glomerulonephritis (20, 12 copies/mL, 8-18), calcineurin toxicity (19, 10 copies/mL, 7-16), interstitial fibrosis/tubular atrophy (12, 10 copies/mL, 9-16) and normal histology (6, 9 copies/mL, 7-16). In the multivariable analysis, absolute and relative dd-cfDNA correlated with the peritubular capillaritis (ptc), glomerulitis (g), and tubulitis (t) scores. In the receiver operating characteristic analysis, absolute dd-cfDNA showed best discrimination for MVI of any cause (area under the curve [AUC] 0.88, sensitivity 0.71, specificity 0.86, positive predictive value [PPV] 0.76, negative predictive value [NPV] 0.82), followed by antibody-mediated rejection including mixed rejection (AUC 0.85, sensitivity 0.72, specificity 0.83, PPV 0.69, NPV 0.84), and overall rejection (AUC 0.83, sensitivity 0.66, specificity 0.85, PPV 0.76, NPV 0.77). T cell-mediated rejection was only detectable by dd-cfDNA when associated with vascular lesions.

Conclusions: Altogether, we conclude that dd-cfDNA-release is not limited to rejection-related injury phenotypes and is mainly driven by MVI in kidney allografts.

Background: Posttransplant lymphoproliferative disease (PTLD) is increased in kidney transplant recipients who are Epstein-Barr virus (EBV) nonimmune (R^-), particularly if the donor has prior EBV immunity (D⁺). PTLD is associated with very high mortality. The purpose of this study was to quantify the impact of PTLD on deceased donor EBV D⁺R^- kidney transplant recipients.

Methods: A Markov model was created to quantify remaining patient life years (LYs) and quality-adjusted LYs (QALYs) in EBV D⁺R^- recipients compared with EBV R⁺ recipients. Different ages at transplant, incidence of PTLD within the first year, potential impact of therapeutic treatments to reduce PTLD, and costs were examined in a sensitivity analysis.

Results: A baseline 40-y-old EBV D⁺R^- recipient is projected to live 21.18 LYs. If there is no PTLD, the recipient lives 21.37 LYs, but if PTLD develops in the first year, the projected life remaining LYs are only 15.03. Each high-risk 40-y-old EBV D⁺R^- recipient loses, on average, 0.192 LYs or 0.134 QALYs. LYs and QALYs gained with prevention depended on the effectiveness of the intervention, incidence of PTLD within the first year, and recipient age. Slightly fewer LYs are lost in younger recipients (age 10 y; 0.156 LF) and older recipients (age 60 y; 0.133 LY), likely due to lower case fatality rates and higher competing risks of death in the young and old, respectively. Strategies, such as rituximab, given at the time of transplant, could be cost-effective (<$50 000/QALY) if the reduction in PTLD was >50% and the cost of the intervention was <$3000.

Conclusions: PTLD has a significant impact on survival in high-risk kidney transplant recipients. Preventive strategies may be cost-effective but would depend on the degree of effectiveness, safety, and cost.

Background: Patients with metabolic dysfunction-associated steatohepatitis (MASH) have distinct medical comorbidities, psychosocial and social determinants of health (SDOH) factors that may impact liver transplantation (LT) rates. The aim of this study was to identify clinical, psychosocial and SDOH factors associated with rates of LT and LT waitlist removal based on MASH etiology.

Methods: This was retrospective cohort study at a large academic transplant center. Adults listed for LT between January 2018 and December 2020 were included. Patients listed as status 1A and those with prior LT were excluded. Demographic, clinical, psychosocial and SDOH characteristics were evaluated. Factors associated with LT and LT waitlist removal were analyzed using univariate and multivariate logistic regression.

Results: A total of 374 patients were included, of which 19% (n = 70) had MASH. MASH candidates more likely to be older (62 versus 57), female (63% versus 35%), and of Latino/Hispanic ethnicity (76% versus 43%). Patients with MASH had significantly lower Stanford Integrated Psychosocial Assessment for Transplant scores, substance use, years of formal education, and private insurance, and had higher percentages of long-term partners. The rate of LT and waitlist removal (including death) did not significantly differ by MASH status. Patients with MASH were significantly more likely to die on the waitlist (62% versus 27%). On multivariate analysis, male sex (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.01-2.92; P = 0.03) and lower Karnofsky score (OR, 0.98; 95% CI, 0.97-0.99; P < 0.01) were independently associated with LT, whereas unemployment (OR, 0.44; 95% CI, 0.23-0.84; P = 0.01) was associated with waitlist removal.

Conclusions: Rates of LT and LT waitlist removal did not significantly differ by MASH etiology, though patients with MASH were significantly more likely to die on the LT waitlist. There continue to be SDOH factors associated with rates of LT, with male sex and employment independently conferring higher odds of access to LT.

Background: The aim of our study is to share our experience with uncontrolled donation after the circulatory determination of death (uDCDD) kidney transplantation and to propose updated donor selection criteria for uDCDD programs.

Methods: A prospective study comparing kidney recipients of grafts from local uDCDD donors with recipients of grafts from local standard criteria donors after the neurological determination of death (DNDD) between 2013 and 2024. Donor acceptance was determined using a combination of 3 factors: donor age, no-flow period, and warm ischemic time (WIT). Normothermic regional perfusion was the preservation method in uDCDD cases.

Results: The study included 43 kidney recipients from uDCDD donors and 80 controls. The median no-flow period was 10 min (interquartile range, 5-13), and the median WIT was 101 min (interquartile range, 86-118). The incidence of delayed graft function was significantly higher in the uDCDD group (46.5% versus 21.3%; P = 0.004), although no significant difference was observed in primary nonfunction rates (2.3% versus 0%; P = 0.35). Long-term outcomes, including serum creatinine levels and estimated glomerular filtration rate at 5 y, were similar in both groups. Graft survival rates at 1 y (95.3% versus 100%) and 5 y (92.1% versus 95%) showed no significant differences between the uDCDD and the DNDD groups. Multivariate analysis revealed that uDCDD kidney recipients did not have a higher risk of graft loss.

Conclusions: Kidney transplantation from uDCDD donors is a viable option, yielding outcomes comparable with those from standard DNDD donors. Strict donor selection criteria and efforts to minimize WIT are essential to achieving optimal long-term results.

Background: India is the third highest in terms of the total number of organ transplants in a year worldwide mainly based on living donor transplants. The number of deceased donor transplants has been limited in India ranking only at the 68th position of 94 countries that reported data to Global Observatory on Organ Donation and Transplantation during the year 2022.

Methods: Representatives of National Organ and Tissue Transplant Organisation in addition to local transplant experts from Northeast India and Indian Society of Organ Transplantation discussed challenges and potential solutions for organ transplantation in Northeast India at the National Organ and Tissue Transplant Organisation session during the India Society of Organ Transplantation 2023 annual conference held at Kolkata.

Results: Here, we summarize deliberations on the opportunities for the care of patients with end-stage-organ failure in India with a focus on the Northeast part of the country. States in the Northeast face many problems for establishing organ transplant programs including but not limited to difficult terrain, lack of skilled healthcare providers (qualified doctors, nursing staff, and technicians) needed for dialysis and organ transplants, financial constraints, administrative issues, limited infrastructure in both government and private hospitals and, in addition, history of lacking support by professional societies. Discussions focused on establishing organ retrieval centers, minimal criteria for starting an organ transplant center, guidelines on how to start a new State Organ and Tissue Transplant Organization, establishing retrieval and transplant centers with support from National Organ Transplant Program, recent reforms in organ donation and transplantation, in addition to overcoming medical, surgical, immunological, administrative, sociocultural, geographic/regional challenges for organ transplantation in Northeast India.

Conclusions: Overall, deliberations aimed at providing a basis for policy makers to start and expand organ transplantation in low and low- to-middle income and infrastructurally poor states.

Background: There is currently a supply and demand mismatch in liver transplantation, with more patients needing transplants than grafts available. The use of older donors is one potential way of expanding access to viable grafts. No national study has yet reported on outcomes of liver transplants with donors ≥70 y.

Methods: The US Scientific Registry of Transplant Recipients registry was queried for deceased donor LT (1988-2021). Balance-of-risk (BAR) score was calculated for each patient. The primary outcome was graft survival. Cubic spline curves were used to evaluate the full spectrum of donor ages.

Results: A total of 148 960 livers met inclusion criteria: 5414 (3.6%) from donors ≥70 y and 4291 (2.9%) recipients ≥70 y. Within the overall cohort, graft survival decreased with increased donor and recipient age. Median graft survival within donors ≥70 y improved over time from 2.2 y (interquartile range [IQR] 0.2-9.8 y) in 1987-1999 to 9.6 y (IQR 3.2-11.6 y) in 2010-2019 (P < 0.0001). Elderly donors had equivalent outcomes to donors <70 y when transplanted in elderly recipients (≥70 y). Outcomes for young recipients that received grafts from elderly donor improved with time, with median survival of 10.1 y (IQR 3.9-11.5 y) in 2010-2019. BAR and survival outcomes following liver transplant (SOFT) scores predicted improved graft survival on time-to-event analysis in all donors aged >70 y. In low-risk recipients, evidenced by preallocation SOFT score <5, elderly donors had comparable outcomes to young (<40 y) and middle-aged donors (40-69 y). Increasing donor age was not associated with worse graft survival in transplants performed between 2010 and 2019.

Conclusions: Donors aged ≥70 y may be more comfortably considered for deceased donor liver transplantation, especially within low-risk recipients. The BAR and SOFT scores may be a useful guide for safely expanding the use of these theoretically riskier liver grafts.

Background: Gastroparesis (GP) is a chronic disorder of the stomach characterized by delayed gastric emptying and frequently associated with longstanding diabetes. This is a single-center retrospective analysis designed to establish the prevalence and assess the impact on posttransplant outcomes of GP among pancreas transplant recipients.

Methods: Medical records for all recipients of pancreas transplants performed between January 2003 and December 2023 were reviewed. GP was defined by abnormal gastric-emptying scintigraphy or other motility study or a history of symptoms. Primary outcomes included graft loss and patient death. Clinical outcomes included length of stay after transplant and readmissions, including specifically for GP symptoms.

Results: Of 731 recipients, 156 (21%) were diagnosed with GP before transplant. Patients with GP were younger and more likely to be female individuals. Posttransplant, there was no difference in length of stay, graft survival, or patient survival. Patients with GP were more likely to be readmitted and to be specifically admitted for GP symptoms. Requirement for interventions was more common in patients with GP.

Conclusions: GP is identified with increased frequency among the specific patient population referred for pancreas transplant, and although it does not seem to affect allograft or patient survival, it does seem to have an impact on readmissions and the need for interventions.

Background: Augmentation of hepatic venous outflow is crucial in living donor liver transplantation (LDLT) to maximize functional graft size and prevent venous complications. We present details of our outflow augmentation technique for left lobe grafts (LLG) in adult LDLTs, which uses all recipient 3 hepatic veins and venoplasty of graft left and middle hepatic veins. This study examines the effectiveness of our technique in preventing outflow complications and the correlation between anatomical variations of the graft hepatic veins and surgical outcomes.

Methods: We retrospectively reviewed 88 patients who underwent LLG-LDLT between 2012 and 2023. The patients were classified into 3 groups based on the graft hepatic vein anatomy and usage of venoplasty: group 1 (n = 10, common trunk without venoplasty), group 2 (n = 62, common trunk with venoplasty), and group 3 (n = 16, no common trunk with venoplasty).

Results: No patient developed clinically significant venous outflow complications or graft loss related to venous outflow. There were no significant differences in complication rates or ascites production among the groups. Five-year graft survival was comparable among the groups (P = 0.43). Multiple regression analysis revealed that the model for end-stage liver disease score was the only independent risk factor for increased ascites after transplant (standardized beta, 0.546; t value,4.20; P < 0.001; 95% confidence interval, 0.287-0.804), but anatomical variations of the graft hepatic veins did not influence ascites output.

Conclusions: The recipient 3 hepatic vein outflow augmentation technique with graft venoplasty can be applied to various graft hepatic venous anatomy and effectively prevents outflow-related graft loss in LLG-LDLT.

Background: In Qatar, the Committee for Oversight of Living Donation (COLD) was established at Hamad Medical Corporation in 2014 to provide standardized, multidisciplinary psychosocial evaluation (PE) for prospective living kidney donors (PLKDs) and ensure appropriate care throughout evaluation, donation, and postdonation follow-up, consistent with legal and ethical standards. We describe the COLD protocol and report PE outcomes of PLKDs in Qatar.

Methods: A retrospective observational cross-sectional study was conducted using case file data of PLKDs assessed at Hamad Medical Corporation between August 2014 and December 2022. Descriptive statistics analyzed demographics and outcomes of COLD evaluation.

Results: Eight hundred ninety-eight PLKDs (54% men) were enlisted for 545 transplant candidates. Four hundred forty-seven PLKDs (49.8%) were Qatari; the remainder were noncitizen residents representing 43 nationalities. Most 680 PLKDs (76%) claimed a genetic relationship with recipients; 20% were emotionally related and 4.34% were unrelated. Of those who proceeded with evaluation, 88% (n = 788) were accepted, 7.5% were declined, and 4.8% dropped out. Of those who were declined (n = 67), 81% were noncitizen residents; 42% claimed an emotional relationship with the intended recipient, whereas 34% were unrelated and 24% were genetically related. The main reasons for declining a PLKD were insufficient socioeconomic support, psychological unfitness, and coercion by employers or family.

Conclusions: Standardized structured PE has been effective in identifying and addressing risk factors across various PLKD demographics in Qatar. This study highlights the importance of comprehensive evaluation for all PLKDs, regardless of nationality or relationships with recipients. The COLD protocol could serve as a valuable tool for PE of PLKDs in other countries.

Background: Sex disparities in solid organ transplantation are well documented. Relative changes in sex-based outcome disparities after the 2017 standardization of simultaneous liver-kidney (SLK) listing criteria in the United States have not been reported. We hypothesized that this policy's objective measures of kidney dysfunction may differentially affect SLK patients by sex and that the use of MELD 3.0 in the SLK population might provide unique benefit to female transplant candidates.

Methods: Organ Procurement and Transplantation Network data were retrospectively analyzed comparing 2013-2016 with 2018-2021 SLK listings. Waitlist outcomes and Model for End-stage Liver Disease (MELD) 3.0 reclassifications were compared by sex and listing period.

Results: There were 2626 and 2609 male patients and 1670 and 1919 female patients pre- and post-policy changes, respectively. The proportion of female SLK listings post-policy change (42.4%) was higher than both female SLK listings pre-policy change (38.9%) and female single-organ liver listings post-policy change (36.8%; P < 0.01). A statistically significant interaction between sex and listing group (pre- versus post-policy change) was present in multivariable analysis (P = 0.02). Female patients were more likely to have a higher MELD 3.0 score than the listing MELD/MELD-Na score when the listing MELD score was <30 (P < 0.01). Among all patients who died on the waitlist, female patients were nearly twice as likely to be underrepresented by listing MELD compared with MELD 3.0 (23% female and 13% male patients; P < 0.01).

Conclusions: Waitlist outcomes were changed differentially between male and female patients after the 2017 SLK policy change. The application of MELD 3.0 to SLK patients is likely to benefit female patients.