Transplantology

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

Background: Artificial intelligence (AI) has rapidly advanced, significantly impacting medicine. ChatGPT, a new AI model, generates responses based on user input. This study evaluates ChatGPT’s ability to assist with pre- and post-kidney transplantation (KT) patient education. Methods: ChatGPT was queried about KT on 21 February 2023 and 2 March 2023. Questions were categorized into general information for pre-KT patients or donors and post-KT patient instructions. Two experts independently assessed the accuracy of ChatGPT’s responses, and the Flesch–Kincaid readability test was applied to evaluate readability. Results: ChatGPT’s responses to general pre-KT questions were clear, concise, and accurate but occasionally misleading. Post-transplant instructions were generally clear and partially concise but lacked supporting evidence. Instructions for emergency situations post-KT were typically safe and reliable, whereas medication-related directions were often inaccurate and unreliable. The mean Flesch–Kincaid readability score was 30, indicating that ChatGPT’s answers were not easy to understand. Conclusion: This study demonstrates that while ChatGPT can provide clear definitions, explain symptoms, and offer reasonable advice on managing medical situations after KT, it frequently gives misleading answers to scientific inquiries. Transplantation researchers and providers should recognize ChatGPT as a potential information source for patients but exercise caution due to its incomplete accuracy and lack of references. Full article

Introduction: Renal parenchymal perforation by ureteral stent placement is a rare but serious complication. There is also a paucity of data regarding collecting system hematomas and potential calcification in renal allografts. Case presentation: We report a unique case of a 51-year-old male who underwent unrelated living-donor kidney transplantation with stent incorporation during ureteroneocystostomy. Post-operatively he was found to have renal parenchymal perforation by the ureteral stent resulting in a pelvicalyceal hematoma with subsequent calcification and obstruction. At the time of guidewire introduction for percutaneous nephrolithotomy one year later, a nephrostogram and passage of a hydrophilic guidewire resulted in improved contrast drainage into the bladder, so the invasive surgery was no longer needed. Discussion: There are few reported cases of renal parenchymal perforation by a ureteral stent, none of which resulted in a collecting system hematoma. The calcification of urinary tract hematomas is also rare and attributed to metabolic abnormalities, prolonged stagnation of blood, and infection. Conclusions: We suspect the nephrostogram and guidewire introduction created enough antegrade pressure and mechanical disruption to force the calcified hematoma into the bladder. Full article

Portal inflow modulation has become standard practice in many transplant centers performing living donor liver transplantation. This is believed to counteract the deleterious effects of excess portal flow into a small-for-size graft. A splenectomy negates the contribution of the splenic vein flow completely and thereby substantially reduces portal inflow. Although it has been adopted as a standard strategy by many Japanese centers for inflow modulation, especially while using left hemiliver grafts, there is justifiable apprehension about its usage due to potential increases in morbidity. Described here is a splenectomy performed while using a modified right hemiliver graft with a graft to recipient weight ratio of 0.49. The challenges in decision making and reasons regarding how such a small graft might have worked without manifestations of small-for-size/flow syndrome are discussed. Full article

Background: Facebook groups have been used to foster social support of transplant patients. Examining the use and content strategies for generating member interactions within transplant-specific groups can inform how we leverage these groups to expand access to social support resources. This study characterizes the use of a closed Facebook group for kidney transplant patient support linked to a hospital in Buffalo, NY to identify the most engaging content. Methods: The sample consisted of 387 individuals (372 patients/family, eight transplant professionals, and seven community advocates) and the administrator. Content analysis was conducted of posts and comments made to the group. Descriptive measures of post content associated with interactions (reactions and comments) were computed. Results: Between 5/2020 and 5/2023, there were 484 posts with 8233 interactions (2793 comments, 5440 reactions). Half of the posts (n = 241) were made by the administrator, 166 (34%) by patients/family, 70 (14%) by community advocates, and 7 (1%) by transplant professionals. Content analysis revealed that post types with the most interactions were personal experiences, monthly transplant volume, and monthly new members added; the least interactions involved posts about holidays, observances, and information. Conclusions: The interaction metrics varied according to the content strategies used by members and provided insights into the types of content members interact with. Full article

Background: Previous data suggested that the outcomes for liver-alone transplant recipients following transjugular intrahepatic portosystemic shunt (TIPS) insertion were comparable to those without TIPS. This study investigates the association between TIPS and outcomes among simultaneous liver–kidney (SLK) recipients in the United States. Methods: Utilizing the Scientific Registry for Transplant Recipients (SRTR) standard analysis file from 2003 to 2022, we examined 9717 adult SLK recipients, among whom 858 had undergone TIPS before transplantation. Kaplan–Meier curves were generated to assess recipient and death-censored liver and kidney graft survival. Mixed-effects Cox proportional hazard models were employed to analyze the association between TIPS and the outcomes of interest, where the transplant center was treated as a random effect. The models were adjusted for recipient age, sex, MELD score, diabetes, duration of listing, induction, steroid maintenance, hepatitis C status, donor age, donor sex, cold ischemia time, local vs. shipped organs, and allocation era. Results: Overall, the two groups were comparable, with minor differences. Notably, the median liver waiting time was significantly longer in the TIPS group compared to the non-TIPS group (4.1 vs. 2 months, p < 0.001). One-year rejection rates for liver and kidney allografts did not differ significantly between groups. Univariable Cox regression analyses demonstrated no association between TIPS and worse outcomes for recipient, liver, and kidney survival (p = 0.65, p = 0.22, and p = 0.54, respectively). TIPS did not emerge as a predictor of recipient or death-censored liver or kidney graft survival in multivariable models. Conclusion: In this extensive national cohort of SLK transplant recipients, pre-transplant TIPS was not linked to adverse outcomes for recipients or their allografts. Full article

Sodium glucose cotransporter type 2 inhibitors are a new class of drugs that act on the cardiovascular system, kidneys and metabolism in a multiple ways. Indeed, even though their principal action involves the transport of sodium and glucose in the convoluted distal tubule, they have multiple actions, such as antifibrotic and endothelial protective effects. Their principal mechanism consists of the loss of sodium and glucose. Therefore, they affect blood pressure and glucose metabolism. Their first use was in the diabetic general population; later, some studies documented their activity in the nondiabetic general population and in heart failure in chronic kidney disease patients. Only in recent years have several small studies documented the efficacy of these drugs in diabetic and nondiabetic kidney transplant patients; relatively large studies are rare, very recent, and open new routes for the development of these drugs. Full article

Background: Healthcare outcomes are influenced by both the effectiveness of healthcare delivery and the health literacy of patients. Patient education materials (PEMs) play a crucial role in disseminating health information to the patients. PEMs need to be at the level of grade six for optimal comprehension across diverse populations. However, that has not been the case in prior studies in healthcare-related fields. We aimed to evaluate the readability status of online PEMs of active adult and pediatric liver transplant institutions. Methods: We used standardized tools to calculate indices, namely Flesch Reading Ease (FRE), Flesch–Kincaid Grade Level (FKGL), Gunning–Fog Score (GFS), Coleman–Liau Index (CLI), and Simple Measure of Gobbledygook for readability assessment. These indices use various measures, like average sentence length, average syllable per word, polysyllable count, and/or average number of letters per 100 words, to determine grade level. Results: The mean reading level of the PEMs was grade 10.73 ± 3.07, corresponding to grade 7 to 14. One-way ANOVA showed no statistically significant difference between these indices (p-value < 0.05). Conclusions: The readability of liver transplant centers’ PEMs exceeded the recommended level, hindering their generalizability to the broader population. This highlights the importance of optimizing the readability of PEMs to improve outcomes for equitable healthcare services. Full article

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