Transplantology

Background/Clinical Significance: Development of acute antibody-mediated rejection (AMR) of allograft is one of the leading causes of mortality in heart-transplant recipients; however, the standard therapy does not always resolve severe forms of rejection. Extracorporeal photopheresis (ECP) is a method of immunomodulatory therapy that involves separating a patient’s white blood cells and treating them with a photosensitizer and ultraviolet A irradiation. Case Presentation: An 18-year-old female patient was urgently hospitalized with complaints of shortness of breath. She had undergone heart-transplant surgery 9 months before due to congenital heart disease restrictive cardiomyopathy, complicated with end-stage chronic heart failure. During the admission she admitted that for 3 weeks she discontinued tacrolimus and mycophenolate mofetil. AMR3 and CAV were verified. Conclusions: The use of standard approaches in the treatment of acute AMR is not always able to suppress an expressed immune reaction against the cardiac allograft, which leads to disruption of its function and rejection in the early or long-term follow-up. The inclusion of ECP in the treatment regimen allowed us to stabilize the patient’s condition and achieve regression in the severity of the AMR. It is believed that an important role in this was played by the activity of the immune system, which we assessed by changing the profile of cytokines, chemokines, and other growth factors. Thus, ECP demonstrated its effectiveness in the treatment of AMR of the cardiac allograft, with a change in the severity of the cytokine storm, as well as with an increase in the contribution of cytokines associated with the Th17 response. Full article

Background/Objectives: This study aims to analyze the short- and medium-term outcomes of lung transplantation (LT) in recipients aged 65 years and older, comparing them with those of younger individuals. The primary endpoints were 90-day and 1-year survival, while secondary measures included perioperative complications and chronic lung allograft dysfunction (CLAD) rates. Methods: A retrospective cohort analysis was conducted on 135 patients who underwent LT at the Siena Lung Transplant Center between January 2013 and December 2023. The participants were stratified into three age groups: under 60 years (Group Y), 60–65 years (Group M), and over 65 years (Group O). Outcomes assessed included ischemia times, transplant type (single or bilateral), ICU and hospital stay, postoperative complications, and CLAD incidence. The data were analyzed using non-parametric statistics, Kaplan–Meier survival curves, and correlation tests between clinical variables and survival outcomes. Results: Among the patients, 88 belonged to Group Y, 36 to Group M, and 11 to Group O. Idiopathic pulmonary fibrosis (IPF) was prevalent in older recipients (82%). Patients over 65 showed a lower prevalence of diabetes (p = 0.025) and pulmonary hypertension (p < 0.01). Bilateral LT was most common in Group Y (91%) and least in Group O (36%, p < 0.0001). Group Y had the longest maximum ischemia time (425 ± 161 min vs. 315 ± 140 min in Group O, p = 0.048). ICU stay (p = 0.289) and hospital stay (p = 0.900) did not differ significantly across groups. No group differences were observed in rates of primary graft dysfunction (p = 0.869), need for renal replacement therapy (p = 0.358), or prolonged ventilation (p = 0.609). CLAD incidence was comparable (p = 0.400), as were 90-day (p = 0.997) and 1-year survival rates (p = 0.174). Conclusions: Carefully selected patients over 65 years old can achieve similar short- and medium-term outcomes to younger LT recipients. These findings support the inclusion of older candidates in transplant programs, while highlighting the need for further research to optimize perioperative strategies and long-term management in this age group. Full article

Background: Transplant ureteral stricture (TUS) reconstruction remains a significant challenge in renal transplantation, particularly when conventional access to the transplant ureter and renal pelvis is not feasible. This report presents two rare and complex surgical reconstructions: a combined calico-vesicostomy and uretero-calycostomy in one patient, and an ileo-calycostomy in another. Both cases involved patients with prior failed minimally invasive interventions and complex anatomy that precluded standard repairs. Case presentation: A hybrid surgical approach incorporating open reconstruction with fluoroscopic and endoscopic guidance was used to access the renal calyces directly, enabling successful re-establishment of urinary tract continuity. The first patient underwent dual reconstruction with native ureteral reimplantation to the middle calyx and a simultaneous calycovesicostomy, bladder to the It lower pole calyx. The second patient, with prior ileal conduit urinary diversion, underwent ileocalycostomy—anastomosing the ileal conduit to the middle calyx. Both reconstructions were performed using modified partial nephrectomies to preserve nephron mass. Long-term follow-up (34 and 40 months) demonstrated excellent graft function and minimal complications. Conclusions: These cases represent the first reported long-term outcomes of calycovesicostomy and ileocalycostomy in transplant ureteral reconstruction and reinforce the utility of calyceal access in complex TUSs. These cases highlight rare but viable surgical options in complex scenarios of transplant ureteral strictures. Hence, a multidisciplinary approach and meticulous preoperative planning are essential to optimize outcomes in these challenging scenarios. Full article

Background/Objectives: To evaluate the impact of the European–Mediterranean Postgraduate Program on Organ Donation and Transplantation (EMPODaT) on organ donation and transplantation (ODT) at 6 years. Methods: EMPODaT is a Trans-European Mobility Programme for University Studies (TEMPUS) project founded by the European Commission to address ODT professionals’ shortage in Middle East/North Africa (MENA) countries through structured postgraduate education. Leading universities from Spain, Germany, Sweden, and France, and key institutions in Egypt, Lebanon, and Morocco, developed a one-year blended training program incorporating e-learning, in-person courses, and hospital traineeships. The effect of the program at 6 years was analyzed by surveying the 90 healthcare participants. Results: A total of 73.9% of respondents remained actively engaged in the field, and some assumed leadership roles (local directors 14.4%, donor coordinators 13%). Also, 65.2% of participants reported improvements in policies and practices, with notable progress in donor screening (39.1%), brain death diagnosis (30.4%), and hospital policy reforms (69.7%). The study identified barriers, such as legal (34.4%), financial (34.8%), and public/social resistance (39.1%). Training alone, without strong hospital policies, support, and government involvement, was insufficient for introducing meaningful changes in ODT. Conclusions: Key aspects for successful implementation of training programs on ODT in MENA countries should consider hospital leadership engagement, strengthen institutional collaborations, and incorporate national health authorities to enhance sustainability and drive systemic changes. Prioritizing individuals in key decision-making positions could further enhance program effectiveness. Full article

Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression. Full article

Background: Graft-versus-host disease (GVHD) is a rare but serious complication following solid organ transplantation (SOT), particularly in transplants involving organs with a high volume of passenger donor T-lymphocytes. This case highlights the clinical course and diagnostic challenges of GVHD following simultaneous pancreas and pre-emptive kidney transplantation. Methods: A 51-year-old male with long-standing type 1 diabetes mellitus underwent simultaneous pancreas and kidney transplantation with induction therapy using rabbit anti-thymocyte globulin and methylprednisolone. Three months post-transplant, he presented with a diffuse lichenoid cutaneous eruption. Diagnostic evaluation included an extensive infectious workup, skin punch biopsy, liver and bone marrow biopsies, and microchimerism assay. Results: Skin biopsy revealed interface vacuolar dermatitis consistent with cutaneous GVHD. Subsequent liver and bone marrow biopsies confirmed GVHD involvement, with microchimerism assay showing 43% donor-origin T-cells in the bone marrow. Initial treatment with systemic and topical corticosteroids led to temporary improvement. However, the patient developed bone marrow suppression, recurrent bacteremia, and invasive fungal infection, resulting in a prolonged ICU stay and ultimately death. Conclusions: This case underscores the importance of considering SOT-GVHD in patients receiving organs rich in donor lymphocytes, such as pancreas transplants. Early recognition and multidisciplinary management are critical to improving outcomes in this rare but life-threatening condition. Full article

Artificial Intelligence (AI) and machine learning (ML) are increasingly being applied across the transplantation care pathway, supporting tasks such as donor–recipient matching, immunological risk stratification, early detection of graft dysfunction, and optimisation of immunosuppressive therapy. This review provides a structured synthesis of current AI applications in transplantation, with a focus on underrepresented areas including real-time graft viability assessment, adaptive immunosuppression, and cross-organ immune modelling. The review also examines the translational infrastructure needed for clinical implementation, such as federated learning, explainable AI (XAI), and data governance. Evidence suggests that AI-based models can improve predictive accuracy and clinical decision support when compared to conventional approaches. However, limitations related to data quality, algorithmic bias, model transparency, and integration into clinical workflows remain. Addressing these challenges through rigorous validation, ethical oversight, and interdisciplinary collaboration will be necessary to support the safe and effective use of AI in transplant medicine. Full article

Background/Objectives: Heart transplantation is a life-saving procedure for patients with end-stage heart failure, yet it involves significant psychological and emotional challenges throughout its various stages. International guidelines recommend a multi-professional approach to the care of these patients and a psycho-social assessment for listing. The recommendations focus on content aspects, but not on the psychometric measure to be administered to patients as part of the assessment. Therefore, the purpose of this study is to provide the preliminary results of administering the protocol used by our center, measuring coping strategies, cognitive functioning, quality of life, and psychological distress in a sample of patients who are candidates for and undergo cardiac transplantation, and to observe any variations after the procedure. Methods: We conducted a comprehensive psychological-clinical assessment involving 40 patients, focusing on psychosocial functioning, cognitive reserves, mental health, and coping strategies. Tools such as the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), Beck Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), General Anxiety Disorder 7 (GAD-7), and Medical Outcomes Survey Short Form 36 (SF-36) were employed to evaluate readiness for transplantation and post-transplant adaptation. Results: Results showed high levels of clinical anxiety (52.5%) and low perceived physical health (98%) before the transplant, while post-operative evaluations indicated reduced anxiety (13.51%) and depressive symptoms (10.81%), along with improved psychological well-being and reintegration into daily life. Conclusions: These results show improvement in physical and cognitive levels, accompanied by a state of enhanced psychological well-being after transplantation. A longitudinal psychological approach, from pre-transplant screening to post-discharge follow-up, is needed to address distress, improve coping mechanisms, and promote treatment adherence. This integrative strategy is critical to improving the quality of life and long-term outcomes for heart transplant recipients. Full article

Background: Primary sclerosing cholangitis (PSC) accounts for 10–15% of liver transplants but is the leading cause of retransplant. This study evaluates whether PSC patients have different survival and graft outcomes when receiving grafts from donors after brain death (DBD) versus circulatory (DCD) death. Methods: Using the SRTR database (2004–2024), we compared PSC patients receiving DCD vs. DBD grafts. Demographics and outcomes including graft loss, mortality, and retransplant were analyzed using multivariable logistic and Cox regression, along with propensity-matched analysis. Results: Among 5762 PSC patients, 391 (6.8%) received DCD grafts. Patients receiving DCD grafts were older but had lower MELD scores (19 vs. 22; p < 0.001) and were less often functionally dependent (11.3% vs. 24.4%; p < 0.001). Multivariable Cox regression demonstrated that receipt of a DCD graft was independently associated with time to graft loss (HR 1.59; CI 1.10–2.31; p = 0.013. Similarly, DCD graft receipt significantly increased the likelihood of requiring retransplant (HR 3.25; CI: 1.93–5.46; p < 0.001) but did not increase the likelihood of mortality. Propensity matched analysis further supported these finding with significantly higher graft loss with DCD grafts at one and two years and higher retransplant rates at all time points including 5-years (+7.9%, CI 4.4 to 11.4%; p < 0.001). Conclusions: DCD grafts in PSC patients are linked to worse graft survival and higher retransplant rates. They may be best suited for older, lower-MELD patients, but further studies on perfusion strategies are needed. Full article

Background: Ischemia–reperfusion injury (IRI) is a key contributor to graft dysfunction in kidney transplantation. Cell-free mitochondrial DNA (mtDNA) is increasingly recognized as a damage-associated molecular pattern (DAMP) and biomarker in IRI, but its prognostic role in living donor kidney transplantation (LDKT) remains unclear. Methods: This post hoc analysis of the VAPOR-1 study evaluated urinary mtDNA (UmtDNA) in 57 LDKT recipients. MtDNA levels (ND1, ND6, and D-loop) were measured at five early timepoints post-transplantation using qPCR. Associations between early UmtDNA and long-term graft function, defined by estimated glomerular filtration rate (eGFR) at 1, 12, and 24 months, were analyzed. Results: Higher UmtDNA levels in the first urine after reperfusion were significantly associated with improved eGFR at 12 months and a positive change in eGFR between month 1 and 24. These associations were not attributable to urine creatinine levels or mitochondrial copy number. Conclusions: In this LDKT cohort, elevated early UmtDNA may reflect a well-functioning graft capable of clearing systemic mtDNA rather than ongoing tubular injury. These findings suggest that the biological interpretation of mtDNA as a biomarker is context-dependent and call for careful reconsideration of its role in early transplant monitoring. Full article

Background: Post-transplant lymphoproliferative disorder (PTLD) encompasses an uncommon but wide spectrum of clinical conditions resulting from abnormal lymphoproliferation in patients receiving chronic immunosuppression following organ transplantation. Undoubtedly, reduced immune surveillance of the Epstein–Barr Virus (EBV) is highly implicated in disease pathogenesis. The incidence of PTLD varies significantly depending upon the organ transplanted, along with the age and EBV serostatus of the transplant recipient. Some programs advocate the use of routine surveillance for EBV in peripheral blood. In the case of liver transplantation, the incidence, clinical features, and outcomes in adult transplant recipients are poorly described. Methods: We performed a single centre retrospective study of 1409 individual liver transplant recipients from 20 June 1988 until 31 December 2024, with a view to describing incidence, clinical and histopathologic features, the impact of EBV, and patient outcomes. Results: There was a 2.0% incidence of PTLD (28 patients). The onset of PTLD was a late clinical event, with a median time of 11.4 (IQR 3.4–6.2) years from transplantation to diagnosis. Most cases were monomorphic PTLD of the diffuse large B cell lymphoma (DLBCL) histologic subtype (85.2%), and the bowel was the most involved organ. EBV was detectable within the tumour in only 52% and within peripheral blood in only 61.5%. Whilst the presence of EBV did not appear to influence the outcome, those patients who were EBV naive at time of transplant, and received an EBV-positive graft, developed PTLD at a significantly earlier post-transplant stage (0.9 years, IQR 0.3–5.8, vs. 11.1 years, IQR 5.5–1.43, p = 0.02). The type of immunosuppression used did not influence the outcome. In addition, 50% of the patients with PTLD died during the study period, at a median of 0.6 (IQR 0.2–2.6) years from disease diagnosis. Conclusions: PTLD remains uncommon in the adult liver transplant population and is usually a late clinical event, with EBV detectable in peripheral blood in only 61.5% of cases. Whilst advocated in some units, routine screening for EBV in peripheral blood is unlikely to be of clinical utility in an adult liver transplant cohort. Full article

Background: Animated video is promising to educate and empower caregiving and provide additional social support for kidney transplant (KT) access; yet, it has not been tested. Our clinical-research group developed a caregiver-directed educational animated video to complement an existing intervention currently being adapted to stimulate social network engagement in KT access. This qualitative study assessed the videos’ learning and sharing applicability to KT caregivers, as well as recommendations for improvement of the video and the transplant centers’ program to meet caregivers’ needs. Methods: Caregivers of KT-seekers (n = 17) and KT-recipients (n = 9) at a single center were individually interviewed after viewing the video remotely on their own device. Interview transcripts were analyzed using content analysis with a deductive approach. Results: Five overarching themes emerged about the caregivers’ perceptions of the animated video: (1) clear and engaging, (2) a good overview of caregiving, (3) a way to refresh knowledge and show others how they can contribute to caregiving, (4) additional information needed, and (5) desired more transplant center communication and support. Conclusions: An animated video to promote caregiving in transplant access was well received as an entry point for education and is potentially applicable for sharing to mobilize additional social support. Full article

Liver transplantation (LT) has deeply transformed the treatment of end-stage liver disease and hepatocellular carcinoma, offering the most effective therapy for many liver conditions. However, LT carries inherent risks, including the development of cancers, which can arise from the transmission of neoplastic cells from the donor, the recurrence of pre-existing cancers, or as a long-term effect of the transplant, originating from the recipient’s own cells. The development of cancer in LT recipients is influenced by a variety of factors, such as age, gender, race, the underlying cause of liver disease, lifestyle factors (like alcohol use and smoking), and the use of immunosuppressive therapy. These combined factors increase the susceptibility of LT recipients to several types of cancer, including skin cancers, gastrointestinal malignancies, and lymphoproliferative disorders. While long-term survival after LT has significantly improved, there has been a notable increase in the incidence of de novo malignancies, which underscores the importance of diligent cancer screening and monitoring in transplant recipients, especially as they age. To manage this increased risk, various screening programs are recommended, including annual skin exams, colonoscopies for patients with primary sclerosing cholangitis (PSC) or inflammatory bowel disease (IBD), and lung cancer screening with low-dose CT for former smokers. When cancer is detected in LT recipients, reducing immunosuppression is a crucial strategy. Decreasing calcineurin inhibitors (CNIs) and integrating mTOR inhibitors (mTORis) provide promising avenues for balancing immunological control with oncological risk. Understanding these risk factors and adjusting immunosuppression appropriately is vital for improving cancer outcomes in LT recipients. Although evidence from LT-specific studies remains limited, insights from other solid organ transplant (SOT) settings, especially kidney transplants, offer valuable guidance in managing cancer risks in LT recipients. This narrative review focuses on the prevention and management of de novo and donor-transmitted malignancies. Full article

Recurrent primary glomerulonephritis is a frequent and severe disease that represents the second or third leading cause of graft loss. The purpose of this study is to address the rates of recurrence for all types of glomerulonephritis, detailing their characteristics and the treatments adopted. The authors collected the main studies and meta-analyses published on PubMed. In addition, the main clinical trials ongoing on the topic were collected. The results highlighted the different frequency of recurrence in relation to the glomerulone-phritis considered, assessing the different characteristics and the different treatments adopted. In conclusion, this review confirms the severity of this disease. The treatment possibilities differ among glomerulonephritis variants. Frequently, a pre-transplant period should be distinguished from a peri-transplant period and a post-transplant period. Fi-nally, new drugs are being discovered to treat recurrent glomerulonephritis and several ongoing trials are also discussed. Some of them have shown important results already. Full article

Objective: This study aims to examine long-term diseases, conditions, self-control, and self-management in kidney transplant recipients. Method: This is a descriptive correlational study, including a total of n = 130 kidney transplant recipients. The data were collected using a demographic information form, the Post-Kidney Transplant Diseases and Conditions Assessment Form, and the Self-Control and Self-Management Scale. Data analysis was conducted using descriptive statistical methods and one-way ANOVA, and paired sample t-tests. Results: Of the kidney transplant recipients, 40% were aged between 31 and 45 years, and 54.6% were male. The long-term diseases and conditions they developed after kidney transplantation were hypertension (46.2%), heart failure (26.2%), diabetes mellitus (10.8%), heartburn (35.4%), acute kidney failure (26.2%), urinary tract infection (39.2%), sleep disorders (23.1%), and chronic pain (50%). In addition, 31.5% of the kidney transplant recipients had poor self-control and self-management. Conclusions: Long-term postoperative mortality in kidney transplant recipients is mostly caused by diseases developing in vital organs. Therefore, it is crucial to recognize these diseases and conditions for their diagnosis. This study found various diseases and conditions in almost all body systems of kidney transplant recipients. Additionally, there were patients with poor self-control and self-management. We consider that the results of our study will increase awareness among clinicians. Full article

Background: Classical Hodgkin lymphoma (cHL) is a treatable malignancy; however, relapsed or refractory (R/R) cases pose significant challenges. PD-1 inhibitors have shown efficacy, but the role of hematopoietic stem cell transplantation (HSCT) following PD-1 blockade remains uncertain. This study aims to evaluate the impact of HSCT after PD-1 blockade on progression-free survival (PFS) and overall survival (OS) in patients with R/R cHL. Methods: We conducted a multicenter, retrospective study involving 42 patients with R/R cHL who received PD-1 inhibitors between 2016 and 2021. Patients were categorized into two groups: those who underwent HSCT after PD-1 therapy (n = 19) and those who continued PD-1 inhibitors without HSCT (n = 23). Results: Among the 42 patients, 27 achieved complete remission (CR) and 15 achieved partial remission (PR) following PD-1 blockade. In the HSCT group, 92% of patients remained progression-free at 3 years, compared to 65% in the non-HSCT group (p = 0.021). OS rates were similar between groups (100% vs. 96%, p = ns). Notably, 80% of PR patients in the HSCT group converted to CR. Relapse rates were significantly lower in the HSCT group (5%) compared to the non-HSCT group (43%, p = 0.005). Conclusions: HSCT following PD-1 blockade enhances PFS in patients with R/R cHL, particularly among those with PR, without offering a significant OS benefit. Further research is warranted to optimize treatment strategies for this patient population strategies. Full article

The growing disparity between the demand for donor hearts and their availability has reignited interest in donation after circulatory death (DCD) heart transplantation. Historically, DCD heart transplantation has been overshadowed by donation after brain death (DBD) due to ethical and preservation challenges. However, recent advancements in procurement techniques allow for evaluation of the donor heart and enable the broader utilization of DCD donors. While challenges remain, early outcomes suggest comparable survival rates between DCD and DBD heart transplantation. This review provides a comprehensive overview of the historical evolution, current practices, and future directions of DCD heart transplantation. Here, we emphasize its potential to expand the heart donor pool and alleviate the organ shortage crisis. Full article