Transplantology

Background: Organ donation is a critical component in the field of transplantation medicine, offering lifesaving opportunities for patients with end-stage organ failure. This study investigated the knowledge, attitude, and practice (KAP) survey regarding organ donation among medical students in Jordan. Methods: A cross-sectional survey was conducted among medical students across six Jordanian universities. Using a convenience sampling method, participants were invited via email, social media, and professional networks to complete a structured online questionnaire. The survey captured data on demographics, knowledge about organ donation processes, attitudes toward organ donation, and self-reported practices. Statistical analyses explored associations between students’ KAP and their demographic characteristics. Results: A total of 539 medical students participated in the study. Findings revealed moderate knowledge and generally positive attitudes toward organ donation, with significant variability influenced by demographic factors. Students from various universities demonstrated different levels of knowledge and attitudes. Notably, religious and cultural beliefs significantly affected students’ attitudes toward organ donation. Conclusions: The study highlighted a gap between the positive attitudes and the actual commitment to organ donation among the participants, revealing a need for targeted educational interventions to address misconceptions and enhance the willingness to donate organs. Promoting organ donation education within medical schools could foster a more supportive environment for organ donation, ultimately contributing to increased donor rates and improved transplantation outcomes in Jordan. Full article

Background: Corneal transplantation faces significant challenges due to the shortage in donor corneas. Porcine corneas have emerged as a potential solution due to their similarities in biomechanical properties with pigs, yet xenoimmune rejection poses an obstacle to their efficacy. Methods: In this study, in silico methods were employed to analyze the compatibility of porcine corneal xenografts, focusing on two key aspects: the comparison of corneal matrix proteins and investigation of the immunological mediators and pathways involved in corneal graft rejection. The amino acid sequences of the fourteen (14) most abundant proteins in the corneal matrix were compared to determine their structural and functional differences. The primary amino acid structures and compositions, theoretical pI, and grand average of hydropathicity were determined and compared between the two species. Results: In graft performance, similarities and differences between the donor and recipient tissues influence the success of transplantation. When the proteins closely resemble each other, in terms of structural characteristics and biochemical properties, the host’s immune system is less likely to recognize the tissue as foreign. The immunological mediators and pathways involved in corneal graft rejection were investigated, elucidating the mechanisms underlying xenograft incompatibility. Based on the results generated from STRING, the specific groups of molecules that are involved in the immune-mediated rejection process are costimulatory molecules, cytokines, immune checkpoint molecules, apoptosis regulators, cell adhesion molecules, growth factors, neuropeptides and hormones, certain receptors, the cytotoxic molecule GZMA, and the chemokine CCL5. Conclusions: The results of this study establish that the porcine cornea has a high suitability for corneal xenotransplantation into humans but requires immune-based therapeutic interventions to increase graft acceptance. Full article

Combined heart-liver transplantation (CHLT) is a viable option for concurrent heart and liver failure, yet its indications are unclear. This preliminary study aimed to describe pre-transplant characteristics and outcomes of patients with liver fibrosis undergoing HT and CHLT, while exploring decompensated liver dysfunction following HT. A total of 52 patients (HT = 42; CHLT = 10) were included. In HT patients, F1 fibrosis was more common (52%), with 43% exhibiting F3 or F4 fibrosis. F4 fibrosis was predominant in the CHLT patients (80%). Post-hepatic portal hypertension was present in 62% of HT and 90% of CHLT patients. None progressed to liver decompensation (i.e., new ascites, variceal bleed, jaundice, hepatic hydrothorax, or hepatic encephalopathy) after HT. Over a median follow-up period of 3.7 [IQR 1.2–9.1] years, the two groups did not differ statistically in survival (p = 0.60). Altogether, HT and CHLT may have similar survival outcomes, and HT patients may not progress to decompensation postoperatively despite advanced fibrosis. Decompensated cirrhosis could serve as a factor for identifying CHLT candidates, but it is crucial to differentiate it from post-hepatic portal hypertension, which does not necessitate liver transplant. Further research is needed to determine selection criteria for CHLT, ensuring efficient utility of organs. Full article

Safely expanding the use of extended-criteria organ donors is critical to increase access to kidney transplantation and reduce wait list mortality. We performed a retrospective analysis of 24 pediatric en-bloc (PEB) compared to 13 dual-kidney transplantations (DKT) and 39 living donor kidney transplants (LDKT) at the University of Virginia hospital, performed between 2011 and 2019. All living donor kidney transplants were performed in 2017. This year was chosen so that 5-year outcomes data would be available. Primary outcomes were glomerular filtration rate and serum creatinine at 12 and 24 months postoperatively. Secondary outcomes were patient and graft survival. The 1-year creatinine levels (mL/min/1.73 m²) were lower in the PEB group (median 0.9, IQR 0.8–1.4) when compared to the DKT (median 1.4, IQR 1.2–1.5) and LDKT (median 1.3, IQR 1.1–1.5) groups (p < 0.001). The 2-year creatinine levels (mL/min/1.73 m²) were also lower in the PEB group (median 0.8, IQR 0.7–1.08) compared to the DKT (median 1.3, IQR 1.1–1.5) and LDKT (median 1.3, IQR 1.0–1.5) groups (p < 0.001). The glomerular filtration rates demonstrated similar results. Graft survival at 1, 3, and 5 years was 100/100/90, 100/92/69, and 96/96/91 for LDKT, DKT, and PEB, respectively (p = 0.27). Patient survival at 1, 3, and 5 years was 100/100/90, 100/100/88 and 100/100/95 for LDKT, DKT, and PEB, respectively (p = 0.78). Dual KT and PEB transplantation are two alternative techniques to safely expand the donor pool. PEB kidney transplantation, though technically more demanding, provides the best long-term graft function. Full article

Chronic kidney disease (CKD) represents a significant global epidemiological challenge, demanding considerable financial resources for treatment. Renal transplantation is the optimal approach for end-stage renal failure, being the most cost-effective option among renal replacement therapies. This narrative review aims to explore clinical conditions associated with excessive healthcare costs among renal transplant recipients, particularly focusing on high-resource users (HRU). We reviewed literature examining conditions generating high costs in kidney transplant patients, including infections, sepsis, pneumonia, antibody-mediated rejection (AMR), graft failure, advanced recipient age, heart failure, and fractures. Immunosuppressive therapies heighten the risk of infections, with sepsis and pneumonia posing significant costs. AMR is a major contributor to healthcare costs, but effective treatment of AMR can extend graft longevity and improve patient outcomes. Graft failure significantly increases medical expenses and adversely affects patient outcomes. Older recipients face higher post-transplant morbidity and mortality rates, though transplantation still offers better long-term survival compared to dialysis. Heart failure and fractures further elevate post-transplant costs and underscore the necessity of targeted interventions to mitigate associated risks. Ensuring kidney transplant care is sustainable and accessible requires a comprehensive strategy. This approach aims to improve patient outcomes while keeping costs reasonable. Full article

The functional outcomes and restoration of form after vascularized composite allotransplantation (VCA) have exceeded the results that could be achieved with current autologous surgical techniques. However, the longevity of VCA grafts has been limited due to the development of donor-specific antibodies (DSAs), and chronic rejection and graft failure occur despite long-term immunotherapy. Furthermore, despite widespread consensus that these non-life-saving transplants are beneficial for select patients, the application of VCA is limited by the need for lifelong immunosuppression. Therefore, attempts to achieve drug-free tolerance through safe and effective therapies are critical. This review highlights recent publications regarding alloantibody-mediated rejection (AMR) in various VCAs with a focus on the critical need for novel tolerance-inducing strategies. The development and implementation of effective methods of inducing tolerance, such as the use of anti-CD3 immunotoxins, could drastically improve VCA graft outcomes and recipient quality of life. Full article

Many patients with a hematologic malignancy have other pre-existing conditions at the time of consideration of an allogeneic stem cell transplant (allo-HSCT). Among these, mild-to-moderate chronic kidney disease (CKD) is a common comorbid condition that can potentially impact the rates of non-relapse mortality among transplant patients. While the risk of severe CKD on allo-HSCT is well recognized, there remains a paucity of data in terms of the impact of mild-to-moderate CKD on patient outcomes in this setting. Using data from the National Inpatient Sample database, we aimed to investigate the impact of mild-to-moderate CKD on hospitalization outcomes for patients undergoing an allo-HSCT. Multivariate analysis revealed that CKD patients had a 31% higher risk of all-cause mortality (OR = 1.31, 95% CI: 1.01–1.70; p = 0.04) and a higher risk of other common hospitalization complications, including acute kidney injury, acute pulmonary edema, cardiac arrhythmias, and septic shock. While this study has limitations, including its retrospective nature and lack of specific medication data, it underscores the importance of considering CKD as a significant risk factor in allo-HSCT outcomes. Full article

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival. Full article

Precision medicine is mainly based on reliable and noninvasive biomarkers. The aim of this review was to describe the newest biomarkers in the field of kidney transplantation and kidney rejection, one of the most common and severe complications. The standard tools used to identify acute rejection largely result in errors and have many drawbacks. In recent years, new and reliable biomarkers have been identified. These methods avoid risks, are noninvasive, and are able to detect rejection even in cases in which acute rejection is clinically asymptomatic and not otherwise identifiable, which is a frequent occurrence. In recent years, several biomarkers have been identified. Very recently, new relevant biomarkers with high positive predictive value and low negative predictive value have been identified. These are the donor-derived cell-free DNA found in the recipient, the gene expression profile of the donor found in the recipient, and the urinary cytokines that are modified in the graft tissue. The aim of this study was to identify the most recent findings in the literature on this topic and to describe the utility and possible limitations of such new biomarkers for kidney rejection. Full article

Hepatic arterio-portal venous fistula (HAPVF) is a rare, abnormal connection between the hepatic artery and portal vein. HAPVFs are usually caused by trauma or hepatobiliary instrumentation. Fistulas can expand and produce symptoms of severe portal hypertension. The decision to embolize should be based on fistula location, size, and symptoms. We report a case of HAPVF in a liver transplant recipient presenting with worsening ascites and variceal hemorrhage after several prior liver biopsies. Given the extensive nature of the fistula and hepatic decompensation, the HAPVF was successfully embolized, resulting in clinical improvement and obviating the need for re-transplantation. Full article

Due to an aging population, advances in multiple medical fields, and shifts among indications for surgery, liver and kidney transplantation is increasingly pursued for elderly patients (aged 65 or greater). Elderly patients represent a uniquely vulnerable group, but overall, they appear to have similar outcomes compared to younger patients. As demographics continue to trend to an older median age, physicians and health care systems must be prepared to take care of elderly transplant candidates. Full article

Histocompatibility testing is pivotal in any renal transplantation workup, aimed at enhancing prospective donor recipient compatibility and improving transplant outcomes. The evolution and advancement of histocompatibility testing, particularly HLA typing, have significantly improved its precision. This study outlines the historical progression from serologic to DNA-based HLA typing, emphasizing the role of HLA proteins in immune response. Anti-HLA antibodies, targeting HLA proteins, pose challenges in renal transplantation. Monitoring and managing these antibodies are critical for renal transplant success. Complement-dependent cytotoxicity crossmatch and flow cytometry crossmatch are essential techniques for assessing donor–recipient compatibility. Panel-reactive antibody assesses antibodies against a panel of donor antigens, often HLA. Higher PRA levels (percentage) complicate donor matching, requiring specialized protocols. Virtual crossmatch evaluates recipient anti-HLA antibodies against potential donors through synthetic beads. This approach predicts crossmatch outcomes by comparing antibody profiles, offering a valuable tool for the risk assessment of renal transplantation. Despite advancements, a comprehensive understanding of alloreactive immune responses requires a combination of assays, emphasizing the importance of a multifaceted approach in histocompatibility testing. This is an attempt to compile the relevant information, providing a basis for comparison in a clear and foundational format for histocompatibility testing laboratories. Full article

In the field of surgery, the idea of performing organ transplants in a minimally invasive fashion has always been a significant technical challenge. The advent of the robotic approach facilitated the overcoming of difficulties in highly complex surgical procedures that demand high technical skill. Furthermore, robotic transplants are showing significant benefits in patient outcomes, particularly in the obese population. The purpose of this review is to provide an overview of the current state of robotics applications for transplant surgery. Kidney transplants were the first to be performed using a fully robotic approach. Since then, robotic surgery has gradually been applied to other organ transplants, with very recent reports of fully robotic lung and liver transplants. Further experiences and studies will be needed to verify their effectiveness and to satisfy some concerns regarding the longer warm ischemia time related to the robotic approach in comparison with open surgery. Full article

Postoperative renal failure significantly impacts long-term renal function and the overall survival of patients receiving liver transplantation (LT), being a crucial factor in their morbidity and mortality. It is difficult to define whether the causes of renal failure are solely related to surgery or anaesthesia during liver transplantation (LT). Indeed, liver disease requiring liver transplantation is often the cause of preoperative renal failure. We report a case of a 62-year-old patient undergoing LT for cholangiocarcinoma that led to acute kidney injury postoperatively while his preoperative renal function was normal. This report highlights the major influence that the surgical and anaesthetic procedure can have on renal function and identifies the factors that may have led to renal replacement therapy being required for this patient. Full article

Kidney transplantation is a life-saving intervention for end-stage renal disease; yet, the persistent gap between organ demand and supply remains a significant challenge. This paper explores the escalating discard rates of deceased donor kidneys in the United States to assess trends, discard reasons, demographical differences, and preservation techniques. Data from the Scientific Registry of Transplant Recipients from 2010 to 2021 was analyzed using chi-squared tests for trend significance and logistic regression to estimate odds ratios for kidney discard. Over the last decade, discard rates have risen to 25% in 2021. Most discarded kidneys came from extended criteria donor (ECD) donors and elevated kidney donor profile index (KDPI) scores. Kidney biopsy status was a significant factor and predictor of discard. Discard rates varied greatly between Organ Procurement and Transplantation Network regions. Of reasons for discard, “no recipient located” reached a high of 60%. Additionally, there has been a twofold increase in hypothermic machine perfusion (HMP) since 2010, with transportation difficulties being the main reason for the discard of perfused kidneys. Our findings suggest a need to recalibrate organ utilization strategies, optimize the use of lower-quality kidneys through advanced preservation methods, and address the evolving landscape of organ allocation policies to reduce kidney discard rates. Full article

The utilization of COVID-19-positive donors has expanded the donor pool for transplantation since the initiation of COVID allograft utilization protocols. However, the biopsy-proven PCR transmission rate of COVID-19 from these allografts has not been well documented. In August 2021, an institutional COVID-19-positive allograft protocol was implemented for liver and kidney transplants. Post-reperfusion liver biopsies were obtained intra-operatively to evaluate for COVID-19 RNA, and post-operative day 7 nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) swabs were collected. The primary endpoints evaluated included COVID-19 RNA on biopsy and COVID-19 detected via nasopharyngeal RT-PCR swab on post-operative day 7. A total of 20 vaccinated recipients underwent transplantation (17 liver only, 3 simultaneous liver and kidney) with whole liver allografts from 20 COVID-19-positive deceased donors between August 2021 and April 2022. 95% (19/20) of donors were asymptomatic at the time of donation. On post-reperfusion liver allograft biopsies, COVID-19 RNA was found in 10% (2/20) of the samples. All the recipients were COVID-19-negative on post-operative day 7 nasopharyngeal RT-PCR, showing a 0% transmission rate of COVID-19 from the positive allografts. The use of COVID-19 allografts appears to be a safe practice, with no PCR-detectable transmission of COVID-19 despite 10% of the liver allografts having COVID-19 RNA present on post-reperfusion biopsy. Full article

There is uncertainty about the best approach to replacement treatment for kidney transplant recipients with chronic terminal graft dysfunction, since a retransplant could be performed before the resumption of dialysis, thus avoiding this treatment and the dilemma of whether or not to suspend immunosuppressive therapy. However, there is limited experience in pre-emptive repeat transplantations, and none from deceased donors. This study aims to assess the results of a pre-emptive retransplantation program with brain-dead deceased donors. We designed a retrospective matched cohort study, including 36 recipients in the pre-dialysis group and 36 controls who were already on dialysis, matched for donor age and transplant date, which could not differ by more than 7 days between pairs. The variables used to standardize the cohorts were donor and recipient age and sex, blood group, duration of the first graft, time on the waitlist to receive the second graft, cold ischemia time, induction and maintenance of immunosuppression, and HLA antibodies (-) prior to retransplantation. The efficacy variables were early graft loss, acute rejection, delay in graft function, renal function at the end of follow-up, survival time, and recipient and graft survival at 24 and 48 months’ follow-up. The pre-dialysis group presented a significantly shorter waitlist time, lower immunization status, and a significantly longer duration of the first graft than the control group. The percentage of recipients who presented early graft loss, delayed renal function, or acute rejection was similar between groups. No significant differences were observed in kidney function or in the survival of the recipient or graft. Retransplantation yields good outcomes in patients with terminal chronic dysfunction, helping to avoid recurrence to dialysis, shortening the time spent on the waitlist, reducing the risk of producing antibodies, and resolving the dilemma of whether or not to stop immunosuppression. Full article

Uterus transplantation (UTx) is a rapidly evolving treatment for uterine factor infertility. New centers offering this treatment must decide whether to utilize living donors, deceased donors, or both. Although limiting UTx to deceased donors eliminates the surgical risks for living donors, an adequate supply of suitable deceased uterus donors in the United States is an emerging concern. Previous studies describing the paucity of deceased uterus donors failed to consider key donor characteristics, potentially overestimating the available organ pool. To estimate the United States’ supply of deceased donor uteri; we extrapolated detailed clinical and demographic information from the regional donor datasets available from three organ procurement organizations to the national Organ Procurement and Transplantation Network donor pool. We estimate there are approximately 3700 possible and 400 optimal uterus donors annually in the United States. Given these projections and the number of women with uterine factor infertility in the U.S. who pursue parenthood through alternative strategies, we conclude that, as uterus transplant transitions from research to established clinical care, demand could quickly exceed the deceased donor supply. The liberalization of deceased donor selection criteria may be insufficient to address this imbalance; therefore, fulfilling the anticipated increased demand for uterus transplantation may require and justify greater use of living donors. Full article

Personality changes have been reported following organ transplantation. Most commonly, such changes have been described among heart transplant recipients. We set out to examine whether personality changes occur following organ transplantation, and specifically, what types of changes occur among heart transplant recipients compared to other organ recipients. A cross-sectional study was conducted in which 47 participants (23 heart recipients and 24 other organ recipients) completed an online survey. In this study, 89% of all transplant recipients reported personality changes after undergoing transplant surgery, which was similar for heart and other organ recipients. The only personality change that differed between heart and other organ recipients and that achieved statistical significance was a change in physical attributes. Differences in other types of personality changes were observed between these groups but the number of participants in each group was too small to achieve statistical significance. Overall, the similarities between the two groups suggest heart transplant recipients may not be unique in their experience of personality changes following transplantation, but instead such changes may occur following the transplantation of any organ. With the exception of physical attributes, the types of personality changes reported were similar between the two groups. These finding indicate that heart transplant recipients are not unique in their reported experience of personality changes following organ transplantation. Further studies are needed to deepen our understanding of what causes these personality changes. Full article