Transplant International最新文献

This study evaluates changes in cellular immunity components, from chronic kidney disease stage V (CKD-V) to long-term transplantation (lKTx). We applied flow cytometry to determine total, CD4⁺, CD8⁺, CD28^- T-lymphocytes, Natural killer cells (NK) and regulatory T-lymphocytes (Tregs), in peripheral blood of 56 patients with CKD-V, 207 patients on hemodialysis (HD), 149 recently transplanted (rKTx), 26 lKTx patients and 49 healthy volunteers as a control group (CG). Lymphocyte proportion decreased in CKD vs. CG [20.2 (14.4-25.8) vs. 29.7 (24.4-38.1)%, p < 0.001] without further deterioration in HD [19.9 (15.3-23.7)%, p = 0.83 vs. CKD-V] and increased in rKTx [24.7 (20-32.6)%, p < 0.001 vs. HD], and lKTx [25.5 (21.9-35)%, p = 0.16 vs. CG]. Similar kinetics were observed in CD4⁺ subpopulations, however CD8⁺ T-cells gradually increased from CG to lKTx. NK remained stable in CKD-V and HD, reduced in rKTx, and marginally increased in lKTx. Tregs gradually declined until HD and suboptimally improved with transplantation. CD28^- subpopulations largely increased in lKTx, compared with HD [CD4⁺CD28^-: 12.6 (4.7-27.6) vs. 6 (2.1-13.2)%, p = 0.006, CD8⁺CD28^-: 68.4 (54.4-90.3) vs. 45.5 (28.4-58.9)%, p < 0.001], independently of age for CD8⁺CD28^- (p = 0.33). Cellular immunity subpopulations show significant changes in the spectrum of CKD, with transplantation restoring total lymphocytes and CD4⁺ T-cells, but not Tregs and NK. LKTx was associated with a large increase in CD28^- subpopulations.

Donor-derived cell free DNA (dd-cfDNA) is an established biomarker for detection of rejection in single organ transplants; data is limited in multi-organ transplant (MOT) recipients. "Use of dd-cfDNA in Multi-Organ Transplant Recipients" (MOTR) was a multicenter, prospective, cross-sectional study that assessed dd-cfDNA fraction (%) and donor quantity score (DQS, cp/mL) in pancreas-kidney (PKT), heart-kidney (HKT), and liver-kidney (LKT) recipients. We explored dd-cfDNA baseline levels across the different organ combinations, and compared them to kidney-only (KT) and heart-only (HT) transplant recipients. Among 347 MOT recipients from 18 sites (PKT = 183, HKT = 57, LKT = 107), most (88.2%) had simultaneous transplants. Median dd-cfDNA levels in PKT and HKT recipients were not significantly different from KT; median dd-cfDNA levels among HKT recipients were significantly higher than in HT recipients (p < 0.001). In LKT recipients, median dd-cfDNA was significantly higher compared to KT (p < 0.001). dd-cfDNA showed associations with organ impairment indicated by abnormal values of pancreatic and liver enzymes in PKT and LKT. As the largest multi-center study to date evaluating dd-cfDNA levels in MOT recipients, MOTR showed that organ-specific physiology affects dd-cfDNA levels across organ transplant combinations, laying the foundation for future efforts to use dd-cfDNA to assess organ-specific signatures of allograft injury in MOT recipients.

The use of extended criteria donors (ECD) has become increasingly important in lung transplantation to address organ donor shortages. To better assess lung graft quality and optimize donor selection, several scores have been developed. This study assesses whether Swiss lung acceptance practice is associated with three validated lung donor scores - the Oto Score, Eurotransplant Score (ET), and Zurich Donor Score (ZDS) - in both DBD and DCD donors. Due to limited clinical data, certain parameters of the Oto and ET Scores were adapted (aOto and aET). Data from 1515 actual deceased donors between 01.07.2014 and 30.06.2024 were analyzed. Logistic regression and AUC-ROC analysis were used to evaluate the scores' discriminative ability. Results showed that all three scores were associated with lung acceptance, with AUC values indicating acceptable to moderate discriminative ability - 0.75 for aOto, 0.70 for aET, and 0.77 for ZDS - and DCD donors being consistently less likely to be accepted for lung transplantation compared to DBD donors. Nonetheless, all three scores showed limitations as standalone models. Developing a novel, nationally applicable Swiss prediction tool integrating current lung acceptance criteria and recipient factors could improve donor-recipient matching, support more efficient organ utilization, and potentially increase transplant activity.

Determination of unacceptable human leukocyte antigen (HLA) mismatches (UAM) before kidney transplantation (KT) aims at minimizing immunological risk and routinely involves Luminex single antigen bead (SAB) testing. SAB-UAM criteria, however, often lack standardization. We implemented standardized mean fluorescence intensity (MFI)-based SAB-UAM criteria in four German transplant centers and prospectively studied the consequences on waitlist composition as well as waiting time, early antibody-mediated rejection (AMR) and graft loss in 267 patients. HLA were deemed unacceptable in case of CDC-reactivity or antibodies against known HLA from previous transplants irrespective of MFI. For all other antibodies, the MFI cut-off was 5.000 with the exception of 10.000 for anti-HLA DQ. We observed significant accumulation of highly sensitized patients (virtual panel-reactivity >95%) on the waiting list during the study period. Median time to KT was longer in patients with UAM, but differences were not statistically significant. Patients with preformed donor-specific anti-HLA antibodies (DSA) below the UAM cut-off criteria (39/267) experienced more AMR episodes compared to DSA-negative patients (10.3% vs. 1.3%, p < 0.001). Graft survival, however, was not statistically different over a median follow-up of four years. Standardized SAB-UAM criteria associated with good short-term outcomes but resulted in accumulation of highly sensitized patients on the waiting list.

Perioperative complications are common in kidney transplantation. Enhanced recovery after surgery (ERAS) is a well-established multimodal perioperative care pathway designed to improve patient outcomes, however, its efficacy in renal transplant remains poorly described. Participating centres included adult renal transplant recipients and 30-day follow-up data. The primary outcome was LOS. Multivariable hierarchical models compared cohorts. 213 patients were included in the study period. 18/23 UK kidney transplant centres were represented. Analysis of the perioperative care delivery demonstrated similar patterns irrespective of reported protocols, with a tendency towards ERAS-type care. Between cohorts, the incidence of complications were similar; formal ERAS 14.3%, ERAS informal 17.0%, no ERAS 12.6%; p = 0.64. Median LOS was also similar; formal ERAS 6.0 days (5.0-11.5), informal ERAS 7.0 days (5.0-10.5) vs. no ERAS 6.0 days (5.0-10.5); p = 0.75. Readmissions were comparable; p = 0.721. Multivariable models confirmed these findings and demonstrated frailer patients had longer LOS and more readmissions. Currently, most UK renal transplant centres deliver a form of peri-operative ERAS care, indicating broad adoption of ERAS principles. Consequently, a formal ERAS protocol is not associated with decreased complications, LOS or readmissions. Efforts to improve outcomes should focus on prehabilitation of at-risk groups on the waiting list.

Antibody-mediated rejection (ABMR) due to non-HLA alloantibodies has gained substantial attention in transplantation research. One candidate for such non-HLA reactivity is the Duffy blood group carrier molecule DARC, which is not only expressed on erythrocytes, but also on kidney microvascular endothelial cells and is postulated as a potential transplantation-relevant alloantigen. However, in vivo observation of anti-Duffy antibodies as trigger of microvascular inflammation (MVI) is lacking. Here we propose a direct relationship between preformed anti-Duffy (anti-Fy^a) antibodies, complement deposition (C4d) in peritubular capillaries (PTC), and MVI. Double immunofluorescence for DARC and C4d in sequential biopsies revealed a striking overlap of DARC expression and C4d staining that was completely restricted to the peritubular capillaries. Remarkably, MVI was confined to PTC with complete absence of glomerulitis and lack of preformed anti-HLA DSA. Retrospective analysis revealed a self-limiting posttransplant flare of a low-level anti-DQ8 DSA after blood transfusions and a high missing-self KIR ligand constellation. Concomitant occurrence of non-HLA and anti-HLA reactivities next to missing-self constellations substantially complicates the assessment of individual contributions for the development and propagation of MVI. Due to the strictly confined distribution of DARC to PTC our report provides in vivo evidence that anti-Fy^a alloantibodies may associate with MVI.

Lungs remain one of the most difficult solid organs for xenotransplantation, owing to its delicate alveolar capillary barrier and intense crosstalk between innate immunity and coagulation system. Multi-gene-engineered donor pig organs combined with co-stimulation pathway blockade based immunosuppressive regimen have extended xenograft survival in preclinical models using non-human primates (NHP) from hours to weeks. Most recently, the first case of lung xenotransplantation into a brain-dead human recipient was reported, confirming technical feasibility without hyperacute rejection while revealing early inflammatory injury and progressive dysfunction. Key barriers include loss of vascular barrier function, dysregulated coagulation and platelet function driven by porcine-human molecular incompatibilities, and antibody-mediated injury. Preclinical data implicate innate immune activation such as natural killer cells and macrophages. Unlike kidney xenotransplantation, which has achieved stable long-term outcomes in NHPs, lungs require attention to immunogenicity against the "fourth antigen" in triple-knockout (TKO) donors that include the positive crossmatch created by the CMAH deletion when TKO organs are tested in NHP. Although consistent multi-month lung xenograft survival has not yet been achieved in preclinical models, the remaining barriers to clinical translation are being defined. This review delineates lung-specific xeno-immune mechanisms and advances aimed at their mitigation, providing insights necessary for future clinical translation.

[This corrects the article DOI: 10.3389/ti.2025.14712.].