Transplantology

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

Background. Recurrent primary glomerulonephritis is a frequent and severe disease that represents the second or third leading cause of graft loss. Objective. The purpose of this study is to address the rates of recurrence for all types of glomerulonephritis, detailing their characteristics and the treatments adopted. Methods: 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 glomerulonephritis 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. Finally, 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

This Critical Appraisal aims to explore the pharmacokinetics and pharmacodynamics of medications used in organ donors after euthanasia (ODE) and their impact on abdominal organ quality. With the legalization of ODE, the donor pool has expanded, but it has introduced complexities regarding organ quality. This study evaluates existing euthanasia protocols in the Netherlands, Belgium, Spain, and Canada, focusing on differences in the medication types and dosages. Additionally, a literature review assessed the potential hepatotoxic effects of high-dose medications like thiopental, propofol, and non-depolarizing neuromuscular blocking agents. High doses of non-depolarizing neuromuscular blocking agents, particularly rocuronium, are associated with hepatotoxic effects in vitro. Furthermore, thiopental doses exceeding 750 mg significantly increase the risk of liver dysfunction. Recent findings also indicate that high-dose propofol and lidocaine can slightly prolong the time to death, which is crucial for optimizing organ viability in ODE. This study highlights the need to optimize organ donation procedures after euthanasia. Further research is needed to achieve this balance, maintaining the integrity and ethical standards of the euthanasia process while enhancing the outcomes of organ donation. Full article

Antibody-mediated rejection is a critical factor in acute and chronic allograft rejection, with Human Leukocyte Antigen as the primary target of the humoral immune response in kidney transplants. In addition to HLA antibodies, non-HLA Abs also play a significant role in AMR. These non-HLA Abs, which can target either autoantigens or alloantigens, may be present pre-transplantation or develop post-transplant. They are associated with various types of allograft injury. The major non-HLA Abs include those directed against the angiotensin II type 1 receptor, endothelin type A receptor, and MICA, as well as other antigens such as vimentin, collagens, and anti-endothelial cell antibodies. Factors such as ischemia, reperfusion injury, and calcineurin inhibitor toxicity can trigger the pathogenic activity of these Abs. The mechanisms underlying non-HLA Ab production are not yet fully understood but are thought to involve endothelial injury and the exposure of neoantigens. Research indicates that these non-HLA Abs can cause graft injury through both complement-dependent and complement-independent pathways. However, detecting non-HLA Abs remains a challenge due to the lack of reliable diagnostic tools. Current treatment strategies for managing the effects of pathogenic non-HLA Abs include intravenous immunoglobulin, plasmapheresis, rituximab, and bortezomib. Early identification of high-risk patients and timely intervention are crucial to preventing graft failure. This review examines the development, mechanisms, and clinical significance of non-HLA Abs in kidney transplantation, highlighting the need for improved diagnostic methods and tailored therapeutic approaches. Full article

Background: Optimizing organ preservation techniques is imperative in the face of donor kidney shortage and high waiting list mortality. Hypothermic machine perfusion (HMP) has emerged as an effective method to improve graft function post-transplantation, particularly for deceased donor kidneys, prone to ischemia reperfusion injury (IRI). The perfusion solution includes glucose to support kidney metabolism; however, its effect on mitochondrial function remains unclear. The present study investigated the effect of glucose supplementation during 24 h of oxygenated HMP on mitochondrial function in porcine kidneys. Methods: After 30 min of warm ischemia, porcine slaughterhouse kidneys were preserved for 24 h using HMP with one of the following three solutions: the standard HMP preservation solution, University of Wisconsin machine perfusion (UW-MP) solution, which contains glucose; the solution used for static cold storage, University of Wisconsin cold storage (UW-CS) solution, which lacks glucose; or the UW-CS supplemented with 10 mmol/L glucose. Tissue and perfusate samples were collected before, during, and after perfusion for further analysis. Results: ATP production, mitochondrial respiration, and oxidative stress markers were not significantly different between groups. Glucose was released into the perfusion solution even from kidneys without exogenous glucose supplementation in the perfusate. Conclusions: These results suggest that kidney mitochondrial respiration does not depend on the presence of glucose in the HMP perfusion solution at the start of perfusion, underscoring the need for further exploration of nutrient supplementation and mitochondrial function in organ preservation strategies. Full article

Background/Objectives: While there are several debates on en bloc renal transplants and pediatric donors regarding the efficacy and concern for renal mass, multiple studies have supported the notion that transplanting pediatric en bloc kidneys produces comparable results in contrast to single kidneys from living or deceased donors. Methods: This case series included a retrospective analysis of a university medical center, primarily focused on comparing the post-operative outcomes between recipients of pediatric and adult en bloc kidneys, which are horseshoe kidneys, from deceased donors and recipients of single adult kidneys from living or deceased donors. Results: This study demonstrated that the post-operative results in recipients of pediatric en bloc kidneys consisting of serum creatinine and estimated glomerular filtration rate (eGFR) values were lower and higher, respectively, and had a comparable improvement in kidney function at post-transplant, 1-week, 1-month, 3-months, and 1-year post-op marks. Conclusions: Our center data and outcomes indicate that en bloc kidney transplantation from pediatric donors yields comparable results to that of single kidney transplantations from living and deceased donors. Full article

Background/Objectives: Kidney transplantation (KT) is the preferred treatment for end-stage renal disease (ESRD), offering improved quality of life, superior survival rates and lower economic burden. However, improving long-term kidney allograft survival post transplantation remains a significant challenge. HLA eplet matching has emerged as a promising strategy to minimize immunological risk and enhance long-term graft survival. Still, our understanding of HLA immunogenicity remains limited. This study aims to evaluate if Electrostatic mismatch score (EMS) and eplet mismatch (EpMM) are significant for predicting KT outcomes and their optimal cut-off values associated with improved graft survival. Methods: Our study analyzed over 10,000 kidney transplant records from the Scientific Registry of Transplant Recipients (SRTR) dataset using traditional survival analysis and machine learning (ML) techniques. The immunogenicity scores EMS and EpMM were calculated based on donor-recipient HLA molecular mismatches. Kaplan–Meier plots, Cox proportional hazards (CPH), random survival forests (RSF), and survival decision trees (SDT) were utilized in assessing the significance of EpMM and EMS in improving KT outcomes and their optimal cut-offs. Results: EpMM and EMS were found to be significant predictors of kidney graft survival. The optimal cutoff values for improved outcomes for EMS and EpMM were 11 and 7 respectively, beyond which graft failure risk increased. The RSF model was the best-performing model in KT outcome prediction (C-index = 0.6945, Brier score = 0.1460). Conclusions: EMS and EpMM were significant in the prediction of kidney transplantation outcomes at cutoffs of 11 and 7, respectively. Incorporating these measures in KT organ allocation strategies could improve long-term survival outcomes. Full article

Background/Objectives: Dual kidney transplantation is a potential technique to reduce the number of discarded kidneys from expanded-criteria donors. Due to allegedly poor outcomes, some centres have abandoned this technique. We aimed to compare dual versus single kidney transplantation. Methods: This retrospective, propensity score-matched, non-inferiority study compared dual kidney transplantation and single kidney transplantation results. Matching was performed based on key donor characteristics, including age, sex, serum creatinine levels, and cause of death due to cerebrovascular accident. The primary outcome was graft survival at ten years post-transplant. Secondary outcomes included overall survival and perioperative complications. Non-inferiority of dual kidney transplantation was defined as a difference in graft survival within a 10% margin. Results: After propensity score, 39 dual kidney transplant recipients were matched with 78 single kidney transplants. Five-year graft survival was 66.1% for dual kidney transplants and 81.3% for single kidney transplants (p = 0.228), and 9-year graft survival was 54.1% dual transplant and 60.8% for single transplant (p = 0.961). There was no significant difference in terms of 10-year overall survival (p = 0.912) either. Surgical times were greater during dual kidney transplants (199.31 ± 49.12 min vs. 129.37 ± 42.11 min, p < 0.001). There were more overall complications associated with dual kidney transplants (35.9% vs. 17.9%, p < 0.05). Conclusions: Dual kidney transplantation achieved non-inferiority for ten-year graft and overall survival, despite higher incidence of complications and longer surgical times. Dual kidney transplantation can be a viable alternative to single kidney transplantation and may increase the pool of potential donors, reducing renal transplant waiting lists. Full article

Background: This study evaluated the outcomes of sutureless small incision Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK-SI) for treating corneal endothelial decompensation. Methods and Analysis: This retrospective study reviewed patients with corneal endothelial decompensation who underwent DSAEK-SI between January 2018 and June 2021 at the Vietnam National Eye Hospital. All patients were followed for at least one year postoperatively. The endothelial graft was inserted into the anterior chamber through a 2.8 mm main corneal incision using a Busin glide. The normal pressure air tamponade of the anterior chamber was applied to attach the graft to the recipient bed. The small incision required no sutures, and no need to remove part of the air from the anterior chamber. This ensured that the surgery ended immediately after the air tamponade, without having to wait for 15 min like with regular DSAEK. The patients were instructed to lie supine for at least 6 h postoperatively. Patients with cataracts underwent combined phacoemulsification and intraocular lens implantation with DSAEK-SI. Results: Sixty eyes from sixty patients were enrolled. The success rate of the surgery was 93.3%. Postoperatively, the best spectacle-corrected visual acuity (BSCVA) improved from 20/3600 to 20/400 at discharge and reached 20/100 at 12 months. Mild astigmatism (0.5D to 2D) was observed in 91.8% of patients, with a mean cylinder of 0.9 ± 0.4D at 12 months. The endothelial cell loss rate after 12 months was 34.6 ± 16%. No graft dislocations or detachments were recorded. Conclusions: The sutureless DSAEK-SI technique with a 2.8 mm incision is a modified technique that achieves high success rates and potentially reduces surgical manipulation and complications. Full article

Background/Objectives: Pneumocystis jirovecii pneumonia is a significant contributor to morbidity and mortality in patients with solid organ transplants. Sulfamethoxazole–trimethoprim prophylaxis has greatly reduced the incidence of this deadly fungal infection. Traditional prophylactic dosing includes single strength (400–80 mg) daily or double strength (800–160 mg) thrice weekly, but is limited by side effects. This study evaluates the efficacy and tolerability of a sulfamethoxazole–trimethoprim single-strength thrice-weekly prophylactic dosing strategy. Methods: This was a single-center, retrospective chart review of 421 patients with 423 total heart transplants at Cedars Sinai Medical Center between July 2016 and June 2020.A total of 361 patients (363 heart transplants) were started on single-strength sulfamethoxazole–trimethoprim thrice weekly for 1 year, based on institutional guidelines. Results: Patients were followed for a median of 3.86 years (range 0.17 to 6.57). Sulfamethoxazole–trimethoprim was started at a median of 7 days (range 0 to 132) for median duration of 11.5 months (range 0.25 to 22). There were no documented Pneumocystis jirovecii pneumonia cases during the study period. At 1 year, 36% of patients had discontinued sulfamethoxazole–trimethoprim. The most common causes for discontinuation were leucopenia (30.8%) and hyperkalemia (2.2%). Conclusions: In our experience, single-strength sulfamethoxazole–trimethoprim thrice weekly for 1 year effectively prevents Pneumocystis jirovecii pneumonia after heart transplant. Further multicenter studies with other patient populations will need to be performed to explore this well-tolerated strategy. Full article

Background: mTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. mTOR-inhibitor (mTOR-I) treatment, either alone or in combination with Calcineurininhibitors (CNIs), significantly reduces the incidence of malignancies after organ transplantation. However, there is no information on which mTOR-I, Sirolimus (SIR) or Everolimus (ERL), has a stronger anti-tumoral effect. Methods: The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 1.164 trials screened, of which 20 could be included (7465 patients). We performed a network meta-analysis to analyze the relative risk of different types of mTOR-I compared to CNI treatment on malignancies after transplantation. A minimum follow-up of 24 months was mandatory for inclusion. Results: Four different types of mTOR-I treatment were analyzed in network meta-analyses—SIR mono, ERL mono, SIR with CNI, and ERL with CNI. The average follow-up of all trials was 43.8 months. All four different mTOR-I regimes showed a significant reduced relative risk for malignancies compared to a regular CNI-treatment with the strongest effect under SIR in combination with a CNI (RR 0.23, CI 0.09–0.55, p = 0.001). This effect remained consistent for all tumor entities except non-melanoma skin cancer (RR 0.25, CI 0.07–0.90, p = 0.033). Conclusions: It is well known that an mTOR-I based treatment in transplant patients reduces the risk of tumor manifestation in comparison to CNI treatment. A combination of SIR and CNI seems to be the most potent mTOR-I therapy against malignancies. Full article

Solid organ transplantation entails numerous complex medical and ethical decisions. Shared decision-making (SDM) has been advocated as the optimal model for navigating these decisions, providing a collaborative framework that enhances person-centered care. This approach involves patients, caregivers, and healthcare professionals in the decision-making process, ensuring that clinical decisions align with patient preferences, values, and individual circumstances alongside clinical indications. This paper reviews the implementation of SDM throughout the transplantation journey, from diagnosis and transplant referral, pre-transplant assessments, waiting lists, to the organ offer, perioperative period, and long-term follow-up. Barriers to SDM include factors at the patient, provider, and system levels, including inadequate patient–provider communication. Effective SDM requires tailored educational resources, prognostic tools, clinician training, collaborative care models, and supportive policies. Additionally, leveraging technology, such as artificial intelligence and mobile applications, can enhance patient engagement and decision quality. SDM promotes equity by involving all patients—including those from more vulnerable groups—in meaningful conversations about their treatment options, thereby mitigating disparities in access and outcomes. Future research should focus on the long-term impacts of SDM interventions, the development of comprehensive prognostic tools incorporating patient-reported outcomes, and systemic changes to integrate SDM into clinical practice, aiming to improve patient outcomes and person-centered care. Full article

Background: The accurate assessment of the glomerular filtration rate (GFR) in potential living kidney donors (PLKDs) is essential for successful transplantation and safeguarding kidney donation practice. Scintigraphy-measured GFR (mGFR) is widely regarded as the clinical reference standard. Various estimated GFR (eGFR) equations, such as the Modification of Diet in Renal Disease (MDRD), Cockcroft–Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, have been developed; however, none have been specifically validated for Vietnamese PLKDs. This study aimed to evaluate the accuracy of eGFR formulas compared to mGFR in PLKDs. Methods: This convenience retrospective study analyzed 189 PLKDs at Cho Ray Hospital in Vietnam from January 2014 to December 2020. The eGFR was calculated using various formulas and compared to the mGFR assessed using ^99mTechnetium-diethylenetriaminepentaacetic acid. Bias, accuracy, and Bland–Altman plots were used to assess the significance of the eGFR values. Results: The median mGFR was 94.20 mL/min/1.73 m² (interquartile range [IQR]: 88.40–100.50). The eGFR values were as follows: 77.52 mL/min/1.73 m² (IQR: 70.50–86.33) for CG; 76.14 mL/min/1.73 m² (IQR: 68.05–83.37) for MDRD; 106.80 ± 15.24 mL/min/1.73 m² for CKD-EPI cystatin C 2012; 96.44 ± 13.40 mL/min/1.73 m² for CKD-EPI creatinine cystatin C 2012; 88.74 ± 13.27 mL/min/1.73 m² for CKD-EPI creatinine 2021; and 101.32 ± 12.82 mL/min/1.73 m² for CKD-EPI creatinine cystatin C 2021. Among these formulas, the CKD-EPI creatinine cystatin C 2012 (P30 = 98.96%) and 2021 (P30 = 97.92%) showed the best consistency with the mGFR, owing to their high accuracy, low bias, and narrow limits of agreement in the Bland–Altman plots. Conclusions: The CKD-EPI equations based on creatinine and cystatin C are reliable tools for donor screening. Full article

Since the success of solid organ transplants, such as human kidneys, livers and hearts, from the 50s to the 60s in the last century, the field of organ transplantation has progressed rapidly. Mainly due to modifications in surgical operation techniques and improvements in immunosuppressive therapy regimes, organ survival time can now be greatly prolonged. This progress has also been dependent upon the availability of appropriate animal models for organ transplantation. Therefore, the mouse heart transplantation model has developed into an irreplaceable research model for solid organ transplantation, providing indelible contributions to the field. In this review, we will provide an overview of the technical developments in murine heart transplantation, as well as its historical and current role for alloimmune research. Further, we will describe its current fields of application and its scientific achievements before we discuss potential future applications. Full article

Background/Objectives: Our study examined 5-year patient and graft survival outcomes among non-smokers, former smokers, and active smokers at the time of liver transplantation (LT) and immediate post-operative complications and short-term outcomes following LT. Methods: This was a retrospective study that examined all liver transplants occurring at Cleveland Clinic Main Campus between January 2015–October 2022. Kaplan–Meier curves examined survival outcomes, and Cox’s multivariate regression analysis was performed. Results: Over the 5-year period, patient survival did not differ statistically between patient groups (all p-values >0.05). However, graft survival was significantly lower in active smokers (p = 0.012). In the multivariate analysis, age (HR = 1.03, 95% CI 1.01–1.05, p = 0.002) and admission to the ICU (HR 1.68, 95% CI 1.13–2.50, p = 0.01) were positively associated with overall mortality. Immediate and short-term complications did not differ statistically between patient groups. Cardiovascular disease (22.5%) was the most common cause of death among all patients. Conclusions: Though our study did not show decreased patient survival outcomes, our findings are in line with previous studies that have shown that pre-transplant smoking is associated with overall reduced graft survival. Combined with the risk for de novo malignancy and cardiovascular events post transplant, smoking cessation before LT should be encouraged to ensure graft longevity. Full article

Background: Kidney Transplant Recipients (KTRs) are at risk of renal cell carcinoma (RCC). The risk of RCC in KTRs is approximated to be 5–10 times higher compared with the general population. A relation between kidney rejection and renal malignancy has been described and relates to the effect of immunosuppression at the genomic level. We decided to investigate any suggestive clinical evidence of this in the OPTN database. Methods: KTRs with de novo RCC between July 2004 and June 2022 were identified. Demographics, baseline characteristics, virology, and immunology data were compared between patients with and without RCC. Our follow-up period was four hundred (400) days. A multivariate regression analysis of the data was conducted. Results: In a total of 215,928 kidney transplant recipients, we identified 839 cases of RCC (0.39%). On multivariate analysis, patients who experienced acute rejection both before hospital discharge (OR 1.559; p = 0.037) and during the follow-up period (OR 1.448; p = 0.002) showed a statistically significant increased risk of developing RCC. Conclusions: Our study is an analysis of a large cohort of KTRs diagnosed with RCC. We observed that RCC appeared more frequently in the kidney transplant recipients that were complicated by acute rejection during transplant admission or follow-up period. Full article