Transplantation Direct最新文献

Background: Adult solid organ transplant recipients (SOTRs) have decreased responsiveness to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination and higher incidence of infection, but there are few data on the serological response in pediatric SOTR. The aim of this study was to determine serological response to SARS-CoV-2 vaccination in pediatric liver (LT) and kidney transplant (KT) recipients and compare it with adult SOTR.

Methods: A European, prospective, multicenter study was performed. Samples were taken at 7 and 32 wk following COVID-19 vaccination and serological endpoints were measured by ELISA.

Results: A total of 42 pediatric (16 post-LT and 26 post-KT) and 117 adult (all post-LT) were included. All pediatric participants and 94% adult participants received mRNA vaccines. Paediatric SOTR patients had significantly higher anti-Spike IgG levels than adult participants at week 7 (114 220.7 [59 285.92-220 058.55] versus 8756.7 [5643.69-13 586.71], P < 0.0001) and week 32 (46 113.2 [10 992.91-193 436.14] versus 8207.0 [3561.20-18 913.43], P = 0.0032). No significant difference in week 7 anti-Spike IgG response was found between pediatric LT and KT (129 434.4 [51 888.64-322 869.69] versus 105 304.5 [39 910.20-277 849.50], P = 0.9854). No differences were seen between children and adults in the rate of decline of anti-Spike IgG between weeks 7 and 32 (P = 0.8000). Male sex and hemolytic-uremic syndrome or postischemic kidney disease were associated with lower anti-Spike IgG levels at week 7 in pediatric SOTR.

Conclusions: Paediatric SOTR demonstrate greater SARS-CoV-2 vaccine responses than comparable adult SOTR patients. These data support efficacy and safety of SARS-CoV-2 vaccination in child SOTR and may alleviate vaccine hesitancy in this patient group.

Background: Organ rejection after solid organ transplantation remains a major challenge. The sentinel skin flap (SSF), a vascularized skin flap procured from the donor and transplanted alongside solid organs, has shown promise for early detection of rejection. The radial forearm free flap (RFFF) has a long history of use in reconstructive surgery and offers distinct advantages as SSF in organ donation procedures (ODPs). Until now, the SSF has been procured using the traditional RFFF way. However, an easier, quicker, and safer way is beneficial for logistical and financial reasons. This study presents a modified RFFF procurement technique for ODPs that is simple, quick, and reproducible and can be executed by surgeons who are not familiar with the original RFFF.

Methods: The traditional RFFF procurement technique was modified using deceased donor models, leading to the development of an SSF technique tailored for application during ODPs.

Results: A modified technique was developed and presented, enabling SSF procurement to be completed within 40 min. During the procedure, the donor's arm was positioned above the head or at a 90-degree angle, allowing the creation of a sterile field without interfering with the anesthesiology or organ procurement team. Donor-site closure was achieved using running sutures, ensuring an optimal cosmetic outcome.

Conclusions: We present a modified RFFF procurement technique, designed to obtain an SSF during ODPs, that we believe can also be executed by surgeons not familiar with this flap, ensuring that the procedure does not interfere with or impede the organ procurement procedure.

Background: Kidney delayed graft function (K-DGF) is associated with worse outcomes in simultaneous pancreas-kidney (SPK) recipients. However, its potential association with specific infections, rejection, and early complications remains unclear.

Methods: We compared recipients with K-DGF to those without K-DGF among all adult SPK recipients transplanted at our center between January 2000 and December 2022 who had >2 wk of pancreas graft survival. Outcomes of interest included common posttransplant infections, including urinary tract infection (UTI), pneumonia, cytomegalovirus, BK, surgical wound infection, infected intra-abdominal fluid collection, graft rejection, and death-censored graft failure (DCGF) within the first year of transplant. We also looked for the need for early laparotomy within 90 d.

Results: Seven hundred sixty-five SPK recipients were included, of whom 85 (11.1%) developed K-DGF. In Cox regression analysis, after adjustment for multiple key variables, K-DGF was associated/related with increased risk for UTI (adjusted hazard ratio [aHR], 1.76; 95% confidence interval [CI], 1.06-0.94; P = 0.03), infected intra-abdominal fluid collection (aHR, 2.14; 95% CI, 1.13-4.04; P = 0.02), and need for relaparotomy within 90 d (aHR, 2.07; 95% CI, 1.27-3.37; P = 0.003). K-DGF was also associated with increased risk for pancreas DCGF (aHR, 4.88; 95% CI, 1.90-12.51; P < 0.001). K-DGF was not associated with risk for other common infections of interest or graft rejection.

Conclusions: K-DGF among SPK recipients is associated with an increased risk of UTI, infected intra-abdominal fluid collection, and the need for early relaparotomy, along with pancreas DCGF. Close monitoring and appropriate management are warranted in this higher-risk patient population.

Background: The relevance of cold agglutinins in lung transplantation (LTx) recipients is unclear. While there is typically no intentionally induced hypothermia, the cold preservation of organs could potentially lead to microvascular injury and vascular occlusion after implantation and reperfusion in the presence of cold agglutinins. This study aims to analyze the impact of cold agglutinins in lung transplant recipients on short- and long-term outcomes after LTx.

Methods: We retrospectively analyzed the medical records of 251 patients who underwent LTx at our institution between March 2003 and June 2023. One hundred seventy-three patients were included in the study. Statistical analysis was performed using SPSS and GraphPad software.

Results: One hundred seventy-three of 251 (69%) of the lung transplant recipients were tested for cold agglutinins, which were positive in 78 of 173 (45%) patients. Most had a temperature amplitude of 4 °C; a broader temperature amplitude was detected in 9 of 78 (12%) patients. While there was no effect on overall long-term survival, cold agglutinins were associated with an increased incidence of reperfusion edema (P = 0.0002), severe primary graft dysfunction grade 2/3 (PGD2/3; P = 0.001), and early postoperative thromboembolism (P = 0.04). Multivariate analysis revealed PGD2/3 and thromboembolism as independent predictors of reduced long-term survival (P = 0.003 and P = 0.003, respectively). Plasmapheresis shortly before LTx in selected patients with a high cold agglutinin titer and broad temperature amplitude removed the cold agglutinins for at least 2 mo with good patient outcomes.

Conclusions: Cold agglutinins are associated with an increased incidence of reperfusion edema, PGD2/3, and early postoperative thromboembolism after LTx. Further studies are warranted to evaluate the benefits of regular screening.

Background: Hydrogen sulfide (H₂S) produced endogenously by the CTH gene-encoded cystathionine gamma-lyase protects from renal ischemia-reperfusion injury in preclinical models. Here, we hypothesized that CTH gene polymorphisms (single nucleotide polymorphism [SNP]) and recipient H₂S serum levels influence kidney graft outcomes after transplantation.

Methods: We included all consecutive recipients of a first kidney transplant in the Swiss Transplant Cohort Study and with available genotyping. In addition, 192 deceased-donor kidney transplant recipients were randomly selected to measure baseline serum H₂S levels. The primary endpoint was graft loss during follow-up.

Results: CTH SNPs were identified in up to 50% of the patients. During median follow-up (6.4 y, interquartile range: 3.9-9.8), graft loss was observed in 247 (9.8%) of 2518 patients. The incidence of graft loss was associated with the presence or absence of CTH SNPs. Specifically, rs672203 and rs10458561, increased the risk of graft loss (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = 0.02; and HR: 1.29, 95% CI: 1.0-1.66, P = 0.05; respectively), whereas rs113285275 was protective (HR: 0.78, 95% CI: 0.6-1.01, P = 0.05). Interestingly, rs672203 was associated with an increased risk of acute rejection (P = 0.05), whereas rs113285275 was associated with a lower risk of acute rejection (P = 0.01). Finally, in patients with delayed graft function, serum H₂S levels correlated with lower graft dysfunction (defined as estimated glomerular filtration rate <30 mL/min/1.73 m²) (P = 0.05).

Conclusions: Graft outcome after kidney transplantation was associated with CTH genotype and, to some extent, H₂S serum levels. Further research is needed to define the underlying protective mechanisms.

Background: Urinary extracellular vesicles (uEVs) are nanosized particles primarily excreted by the kidney. Kidney-derived uEVs (kd-uEVs) are promising noninvasive biomarkers for assessing kidney allograft health and diseases such as acute rejection (AR) after kidney transplantation. However, their release dynamics posttransplant are unclear. This pilot study investigates kd-uEV dynamics and their potential to distinguish AR from acute tubular necrosis (ATN) and nonbiopsied controls.

Methods: In the discovery cohort, urine samples from 72 donor-recipient pairs were collected pretransplant and on posttransplant days 3, 7, 180, and before for-cause biopsies. A validation cohort included 28 recipients biopsied within the first 2 wk posttransplant. Urine was stained with CD63 (uEV marker) and kidney-specific markers aquaporin 2 (AQP2) or podocalyxin (PODXL). Kd-uEVs were quantified using imaging flow cytometry, and percentages among total CD63⁺ uEVs were calculated to adjust for urine dilution.

Results: The percentage of kd-uEVs was lower in pretransplant recipients (AQP2⁺: 1.1% [Q1-Q3, 0.3%-1.7%]; PODXL⁺: 1.5% [Q1-Q3, 0.9%-2.8%]) compared with donors (AQP2⁺: 4.7% [Q1-Q3, 0.9%-11.5%], P < 0.001; PODXL⁺ 6.4% [Q1-Q3, 1.4%-9.8%], P < 0.01). Recipients' kd-uEVs remained on pretransplant levels on posttransplant day 3 but were higher on day 7 (AQP2⁺: 7.2% [Q1-Q3, 2.6%-17.4%], P < 0.001; PODXL⁺: 10.0% [Q1-Q3, 3.2%-16.3%], P < 0.001) and persisted until day 180. In the initial 2 wk after transplantation, AR cases had higher AQP2⁺ kd-uEVs (17.6% [Q1-Q3, 8.6%-32.3%]) than nonbiopsied controls (6.8% [Q1-Q3, 2.1%-11.2%], P < 0.05) and ATN (1.6% [Q1-Q3, 0.5%-6.4%], P < 0.01), with similar observations for PODXL⁺ kd-uEVs. This difference between early AR and ATN was validated in the validation cohort.

Conclusions: Kd-uEV release is prominent from day 7 posttransplant. Elevated kd-uEVs are associated with AR, distinguishing it from ATN and demonstrating their potential as noninvasive biomarkers for early AR diagnosis.

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: 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: 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.