Transplantology doi: 10.3390/transplantology7020010

Authors: Balázs Nemes Ákos Szeredi Zsolt Abonyi-Tóth Orsolya Balogh Aranka Dimovics Dóra Fazekas Edit Szederkényi

Background/Objectives: Given the narrow therapeutic range of tacrolimus and substantial inter-individual variability in trough levels, both total daily dose and the trough level-to-dose ratio are commonly used to guide dose optimization. In this study, Life-Cycle Pharma tacrolimus was compared with immediate-release tacrolimus in a real-world setting. Methods: This longitudinal observational study included kidney transplant recipients at two Hungarian university clinics. Sixty-three (63) patients completed the study and were included in the statistical analysis. They received either Life-Cycle Pharma-tacrolimus (n = 40) or immediate-release tacrolimus (n = 23) as maintenance therapy in the two study arms, each combined with everolimus or mycophenolic acid and corticosteroids. Patients were enrolled 4–6 weeks after transplantation and prospectively followed for 48 months. Tacrolimus trough level, total daily dose and their ratio were recorded at each of the seven follow-up visits during the 48-month study period. Epidemiological data, patient characteristics, laboratory parameters (including eGFR, de novo donor-specific antibodies, and CMV and BK virus incidence), and acute rejection episodes were monitored. Results: The mean age at enrolment was 53.35 years, and 41 patients (65.08%) were male. A stable therapeutic maintenance trough level was achieved in both study arms. Life-Cycle Pharma tacrolimus required a 30% lower total daily dose than immediate-release tacrolimus to achieve comparable exposure. A gradual decline in eGFR was observed in the immediate-release tacrolimus arm (a mean decrease of 6.06 mL/min/1.73 m2 over 4 years) from a baseline level of 58.52 mL/min/1.73 m2 (±16.69), whereas GFR increased in the Life-Cycle Pharma tacrolimus arm (a mean increase of 4.76 mL/min/1.73 m2 over the same period) from a significantly lower baseline level of 46.55 mL/min/1.73 m2 (±17.04). Conclusions: Both formulations provided effective long-term maintenance immunosuppression in kidney transplant recipients and maintained stable trough levels. Life-Cycle Pharma tacrolimus represents a potential option for dose minimization, and it also helped to stabilize renal function despite the worse baseline condition.

Transplantology doi: 10.3390/transplantology7020009

Authors: Takashi Inoue Masayuki Chida Yoshinori Okada Masaaki Sato Hidemi Suzuki Yasushi Hoshikawa Toyofumi Chen-Yoshikawa Daisuke Nakajima Yasushi Sintani Shinichi Toyooka Seiichiro Sugimoto Toshihiko Sato Takeshi Shiraishi Keitaro Matsumoto Takahiro Nakajima Sumiko Maeda

Background: Recently, there has been a dramatic increase in deceased lung transplantation (DLT) procedures performed in Japan. However, there is concern that the number of transplantations may reach the limit of capacity in some centers. The present study was conducted to analyze the relationship between the numbers of individuals registered for DLT by the Japan Organ Transplantation Network (JOT) and procedures subsequently performed at lung transplantation centers. Methods: Using a database and registry reports provided by the Japanese Society of Lung and Heart-lung Transplantation, the numbers of individuals registered in the JOT and DLT procedures performed from January 2014 to December 2023 were analyzed. Results: The number of registrations was found to be correlated with the number of DLTs, with the coefficient of determination (R2) 0.962 and slope of the regression line (X coefficient) 0.407. The facility with the greatest number of registrations, with a registration-to-transplantation ratio of 0.353, was identified as an outlier (p < 0.05) and excluded from analysis. This exclusion increased both the correlation coefficient value to 0.986 and X coefficient value to 0.461. Conclusions: The present analysis showed that the number of DLTs was well correlated with number of registrations at each of the transplantation facilities. Both registration and transplantation numbers have increased in the recent decade. The facility with the highest number of registrations showed a lower registration-to-transplantation ratio, because the increase in registrations outpaced the number of transplantations.

Transplantology doi: 10.3390/transplantology7010008

Authors: Khanh Ba Nguyen Ha Khanh Nguyen Que Ngoc Tran Linh Quang Do Thanh Ha Nguyen

Background: In countries lacking donor registries, related donors, including haploidentical ones, often serve as the main option. This research aimed to examine the feasibility of locating donors for allogeneic hematopoietic stem cell transplants and to assess the outcomes associated with various donor types. Methods: Between 2019 and 2024, a retrospective observational study was carried out, involving 520 patients and 824 potential stem cell donors. Of these patients, 155 successfully identified a suitable donor and underwent allogeneic stem cell transplantation using mobilized peripheral blood stem cells. The study tracked overall and event-free survival over a five-year period to assess outcomes based on different donor types. Results: With alternative related donors (ARDs), 91% of patients were able to find at least one suitable donor for transplantation. The chances of identifying an appropriate donor increase with a larger pool of potential donors. Transplantation outcomes using ARDs, such as siblings, children, or parents, were similar to those with matched sibling donors. Other relatives could be considered as potential haploidentical donors, but the results with these donors were less favorable compared to those of others. Conclusions: The use of ARDs has significantly expanded the availability of related donors, with promising outcomes.

Transplantology doi: 10.3390/transplantology7010007

Authors: L. Annick van Furth Dafni Efraimoglou Albert Gerding Barbara M. Bakker Peter Olinga Henri G. D. Leuvenink Leonie H. Venema

Background/Objectives: Kidneys from marginal donors are more susceptible to ischemia–reperfusion injury (IRI). To diminish the deleterious effects of IRI, mitochondria should be preserved optimally between donation and transplantation. It is unknown which macronutrients are imperative to support mitochondrial function during normothermic preservation. The aim of this study is to investigate the effect of different macronutrient compositions on mitochondrial function during prolonged normothermic incubation of precision-cut kidney slices. Methods: Both porcine (n = 8) and human (n = 5) kidneys were studied. After warm ischemia and cold preservation, precision-cut kidney slices (PCKS) were made and incubated in different incubation media under normothermic conditions. PCKS were incubated with all different combinations of glucose, glutamine and/or fatty acids. At zero, 24 and 48 h, mitochondrial function and metabolite levels were assessed. Results: After 48 h of incubation, ATP levels were significantly higher with glucose and glutamine or fatty acids and glutamine, compared to incubation without nutrients (p = 0.001 and p = 0.003, respectively). Also, mitochondrial oxygen fluxes were higher with all nutrients compared to no nutrients (ADP stimulated basal respiration p = 0.040; proton leak p = 0.001 and maximal respiration p = 0.039). Conclusions: The addition of multiple macronutrients during prolonged normothermic incubation increases the mitochondrial function of PCKS. These data pave the way for optimising the nutritional support for ex vivo perfusion of marginal kidneys.

Transplantology doi: 10.3390/transplantology7010006

Authors: Hatice Gülsoy Hatice Öntürk Akyüz

Background: This study was conducted to guide researchers by providing a global macroscopic perspective on the main characteristics of publications on nursing care in patients undergoing organ and tissue transplantation. Methods: The data obtained from the Web of Science (WoS) database in light of the determined keywords were analyzed using quantitative and qualitative criteria. The bibliometric analyses and visualizations were conducted using Microsoft Excel 365, VOSviewer (version 1.6.20), and the Biblioshiny interface within the R environment. Results: A total of 525 records were initially identified from the Web of Science database. After excluding meeting abstracts, editorials, and letters to ensure data quality, 411 publications (articles and reviews) were included in the final bibliometric analysis. The majority of these publications (87.6%) were published after 2005. The top five countries with the highest number of publications are the United States (USA), Brazil, China, Turkey, and Australia. Conclusions: This study is the first bibliometric analysis study to examine the trend of scientific publications indexed in Web of Science for nursing care in patients with organ and tissue transplantation processes. The findings have the potential to be used to improve the work of scientists conducting research in the field of nursing care.

Transplantology doi: 10.3390/transplantology7010005

Authors: Mahmoud Elshehawy Safa Elmakki Hana Morrissey Patrick Anthony Ball

Background: Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody directed against the 21–28 kd cell surface glycoprotein, CD52. Alemtuzumab is used as an organ anti-rejection therapy in transplant recipients. Neuro-ophthalmic adverse effects are rarely described, and, to our knowledge, accommodative spasm has not previously been reported in a transplant recipient. Case Description: A thirty-nine-year-old woman with genetically confirmed NPHP1-associated nephronophthisis, with stage F3 fibrosis, developed persistent bilateral blurred vision 72 h following alemtuzumab administration for a biopsy-proven acute cellular rejection, approximately six to seven weeks post-transplant. Initial attribution to hyperglycaemia and tacrolimus toxicity delayed recognition. Cycloplegic refraction confirmed a marked hyperopic shift (+2.75 D right eye, +2.50 D left eye) with significant improvement in visual acuity, consistent with accommodative spasm. Systemic evaluations excluded hyperglycaemia-related lens changes, calcineurin inhibitor neurotoxicity, and cytomegalovirus retinitis. MRI was not pursued in the absence of red flag neurological features, and because a definitive ophthalmic diagnosis had been made. Management and Outcome: The patient was managed expectantly, as cycloplegic refraction had already confirmed the diagnosis, and symptoms were improving. Therapeutic cycloplegia (e.g., atropine) was withheld to avoid impairing near vision and driving ability. Full resolution occurred within 4 to 6 weeks without intervention. Drug exposure to onset of symptoms was 72 h; onset of symptoms to diagnostic confirmation was 22 days; total symptom duration was 5.5 weeks, and recovery was 2 weeks after diagnosis. Conclusions: This case represents the first reported transplant case of alemtuzumab-associated accommodative spasm. Causality assessment supports a WHO-UMC classification of “Probable”, aligning with five Bradford–Hill considerations (temporality, biological plausibility, consistency, specificity, and analogy), but without statistical “strength of association” given that this is a single case report. Early cycloplegic refraction should be incorporated into the evaluation of post-alemtuzumab visual complaints, and clinicians should contribute to pharmacovigilance through structured reporting to capture these rare but important events.

Transplantology doi: 10.3390/transplantology7010004

Authors: Jorge de la Mata Oleksandr Boiko Sofia Zarraga Jorge Garcia-Olaverri Ana Llorente Sergio Prieto David Lecumberri

Background/Objectives: Incisional hernia (IH) is a frequent complication after kidney transplantation, with its risk influenced by both patient-related factors such as obesity, diabetes mellitus, and smoking, and procedure-related factors including surgical technique and immunosuppressive therapy. This study aimed to identify risk factors associated with IH and to evaluate the impact of suture type used for fascial closure in kidney transplant recipients. Methods: We performed a single-center retrospective case–control study including adult kidney transplant recipients who underwent transplantation between January 2014 and January 2024. Patients who developed an IH were identified and matched 1:6 with controls according to year of transplantation. Demographic variables, patient comorbidities, dialysis modality, and type of fascial closure suture were analyzed. Patients were subsequently compared according to the type of fascial closure used, either absorbable barbed polydioxanone sutures or absorbable monofilament polyglyconate loop sutures. Multivariable logistic regression analysis was conducted to identify independent predictors of IH. Results: Among 1586 kidney transplant recipients, 39 patients developed an IH, corresponding to an incidence of 2.5% after a median follow-up of 36 months. On multivariable analysis, age was independently associated with IH development (OR 1.04; p = 0.01), as was obesity (body mass index > 30 kg/m2; OR 2.55; p = 0.01). The overall incidence of IH did not differ significantly between suture types, with rates of 11.4% (10/88) for absorbable barbed polydioxanone sutures versus 15.6% (29/186) for absorbable monofilament polyglyconate loop sutures (p = 0.35). In obese recipients, however, fascial closure with barbed polydioxanone sutures was associated with a significantly lower incidence of IH, at 9.1% (2/22) versus 36.4% (12/33) for loop sutures (p = 0.02). Conclusions: Obesity and older age were the main independent predictors of IH after kidney transplantation in this cohort. In obese recipients, fascial closure using absorbable barbed polydioxanone sutures was associated with a substantially lower IH rate. These findings warrant confirmation in prospective, randomized studies.

Transplantology doi: 10.3390/transplantology7010003

Authors: Jacobus W. Mensink Jacob K. de Bakker Marko J. K. Mallat Milou van Bruchem Danny van der Helm Marieke van Meel Aiko P. J. de Vries Robert A. Pol Christian Margreiter Volkert A. L. Huurman

Introduction: While extensive research has been conducted on specific factors affecting transplant outcomes in simultaneous pancreas-kidney recipients, less is known about outcomes following single pancreas transplantation (PTx). This study focuses on identifying factors related to early graft loss after PTx. Patients and Methods: A retrospective analysis was performed on a Eurotransplant (ET) registry database encompassing all consecutive solitary pancreas transplantations from 2000 to 2018. To address any missing values, multiple imputation techniques were employed. Uni and multivariable statistical analyses were performed. Results: The primary causes of early graft loss (<90 days) were thrombosis, bleeding, rejection, and infection. Using multivariable analysis, donor male gender (Hazard Ratio (HR) 0.62) was significantly associated with early graft survival. Of all recipient variables, recipient age (HR 0.96) and recipient cardiovascular history (HR 2.10) were associated with graft loss. A subgroup analysis PTx of female donors into female recipients showed an increased risk for early graft loss compared to male-to-male transplants (HR 2.14). The graft survival rates were 62.9% and 79.0%, respectively (p = 0.017). Discussion: This Eurotransplant registry analysis identifies various donor- and recipient-related risk factors after PTx, partly mirroring the SPK population but also identifying new factors. These findings identify PTx patients as a separate entity in pancreas transplantation and emphasize the need for tailor-made matching of donors and recipients.

Transplantology doi: 10.3390/transplantology7010002

Authors: Josip Basić Ivan Romić Juraj Kolak Goran Pavlek Hrvoje Silovski

Liver graft shortage remains a major limiting factor in contemporary liver transplantation, particularly in the setting of increasing waiting list pressure and constrained donor availability. While the biological quality of donor organs cannot be modified surgically, several operative strategies have been developed to optimize liver utilization and compensate for insufficient graft volume. These include split liver transplantation (SLT), dual-graft living donor liver transplantation (DGLT), auxiliary procedures, and selected multi-graft or hybrid configurations. This review provides an updated and structured overview of surgical concepts aimed at maximizing effective liver mass for transplantation. We discuss indications, technical considerations, and reported outcomes of split, dual, and combined graft approaches, with particular emphasis on graft-to-recipient weight ratio (GRWR), portal inflow modulation, and prevention of small-for-size syndrome. The role of machine perfusion technologies—including normothermic and hypothermic approaches—as enabling tools for graft assessment and safer utilization of partial grafts is also examined. Finally, we address ethical and logistical challenges associated with complex graft strategies and outline future directions in which advances in perfusion, graft assessment, and staged transplantation concepts may further refine patient selection and procedural safety. Collectively, these strategies represent complementary solutions for extending liver transplantation beyond conventional single-graft paradigms in highly selected settings.

Transplantology doi: 10.3390/transplantology7010001

Authors: Yi-Meng Wang Zhao-Zu Feng Fan Mu Bo Wang Liang-Shuo Hu

Background: Chyle leakage is known to be a rare postoperative complication following liver transplantation (LT), and continuous leakage of large volumes of chyle can worsen prognosis. However, its mechanism is not fully understood, and no existing reports show the influence of chyle leakage after LT on blood concentration of the drug tacrolimus. Case presentation: A 43-year-old male with primary hepatocellular carcinoma (HCC), decompensated cirrhosis, and massive ascites underwent orthotopic liver transplantation (OLT). During active chyle leakage, his daily tacrolimus dose was escalated to 4.0 mg with concurrent administration of a CYP3A5 inhibitor, but blood concentrations remained subtherapeutic (1.7–2.5 ng/mL). Conservative treatments failed, so intraperitoneal injection of erythromycin (0.75 g) dissolved in 25% glucose solution (40 mL) was initiated on postoperative day (POD) 11, then administered every other day. After three treatments, chylous drainage reduced significantly, and tacrolimus concentrations abruptly increased to 14.7 ng/mL following a marked reduction in chylous drainage (to 800 mL/d on POD 13). Subsequent dose adjustments stabilized tacrolimus levels at 4.6–6.2 ng/mL with a daily dose of 2.0 mg. Conclusions: Intraperitoneal injection of erythromycin hypertonic solution may promote lymphatic fistula closure via chemical stimulation, though its efficacy requires further validation. Chyle leakage likely reduces tacrolimus blood concentration through multiple potential mechanisms. This case highlights the need for clinical attention to the association between chyle leakage and immunosuppressant concentrations, though further studies are required for validation.

Transplantology doi: 10.3390/transplantology6040038

Authors: David Adandedjan Igor Gala Rastislav Kalanin Tatiana Baltesova Jana Katuchova Luboslav Bena Stefan Hulik

Background: Minimally invasive techniques for living donor nephrectomy are crucial for donor safety and promoting organ donation. Hand-Assisted Retroperitoneoscopic Donor Nephrectomy (HARP-DN) combines the benefits of minimally invasive surgery with the tactile feedback of open surgery. This study analyzes a single center’s initial experience with this technique. Methods: A retrospective analysis was conducted on the first 50 consecutive living kidney donors who underwent HARP-DN at our institution. We collected and evaluated preoperative demographics, intraoperative data (operating time, warm ischemia time), and postoperative outcomes, including complication rates, length of hospital stay, and donor renal function at discharge. Results: All 50 HARP-DN procedures were successfully completed with zero conversions to open surgery and no donor mortality. The mean operating time was 192.4 ± 57.7 min, and the median warm ischemia time was a competitive 110 s. The overall perioperative complication rate was low at 4% (2/50 cases), involving manageable bleeding events. Donors experienced a rapid return to oral diet, and all were discharged with excellent renal function as indicated by a mean serum creatinine of 1.09 ± 0.30 mg/dL. Conclusions: Our initial experience demonstrates that Hand-Assisted Retroperitoneoscopic Donor Nephrectomy is a safe, reproducible, and effective procedure. It offers the advantages of a minimally invasive approach, including low morbidity and excellent preservation of donor renal function, while achieving a short warm ischemia time critical for graft quality. These findings support HARP-DN as a safe, reproducible, and effective option for living donor nephrectomy.

Transplantology doi: 10.3390/transplantology6040037

Authors: Aigul Brimova Anastasia Ganina Larissa Kozina Daulet Berikbol Manarbek Askarov Yerzhan Shayakhmetov

Background: Lung cancer is one of the leading cancers worldwide in mortality and incidence. Treating advanced stages of lung cancer is a great problem because of high metastatic potential and low adherence to common monotherapies such as radiation or chemotherapy. In addition, monotherapy in aged patients is not always sufficiently effective. Case Report: This study presents a clinical case of a 71-year-old man with an advanced stage of lung cancer. Computed tomography (CT) of the chest revealed central tumor of the left lung and moderate mediastinal lymphadenopathy. We found circulating tumor cells (CTC) in the peripheral blood of the patient at the level of approximately 19 cells per 1 mL above the referent detection limit. The patient was treated with combined tomotherapy (eight fractions, one fraction per day except weekends) and immune cell therapy using autologous activated lymphocytes (twice during the period, on tomotherapy day #1 and day #6). The lymphocytes were obtained from peripheral blood, purified, pre-activated in culture with a specific combination of cytokines, and infused back into the patient seven days post-culture. Two months post-therapy, the tumor was reduced by 42.5% in linear dimensions according to RECIST and by 78% of volume compared to the initial values, as confirmed by CT examination. Additionally, the level of CTC in the peripheral blood dropped to the referent detection limit. Conclusions: The combination of tomotherapy and immunotherapy with activated autologous lymphocytes may result in the positive dynamics of the malignant condition in selected patients, even in aged ones.

Transplantology doi: 10.3390/transplantology6040036

Authors: Bilsev Demir Semra Bulbuloglu Kubra Kayaoglu

Purpose: This study aimed to examine post-traumatic growth, mindfulness, and quality of life in recipients after liver transplantation. Design and Methods: This study employs a descriptive and cross-sectional design. We collected data in an organ transplant center affiliated with a research and application hospital in Eastern Turkey. The sample in our study included a total of 292 liver transplant recipients. We collected data using a personal information form, the Post-Traumatic Growth (PTG) Inventory, the Mindfulness Scale (MS), and the Quality of Life Questionnaire (QoL) Short Form (SF-36). We performed data analysis using descriptive statistical methods and one-way analysis of variance. Results: Of the liver transplant recipients, 72.6% were between 45 and 64 years of age, 72.3% were female, and 56.5% had undergone liver transplantation more than 1 year prior. Liver transplant recipients scored between 64.89 and 97.85 on the negative subscales. Recipients scored between 32.70 and 44.72 on the positive subscales in QoL SF-36. The PTG and MS mean scores were 62.43 ± 20.31 and 62.35 ± 7.14, respectively. There was a positive correlation between positive QoL sub-dimensions and MS and PTG (p < 0.05). Conclusions: We found a positive and strong relationship between PTG and mindfulness; in addition, we found that an increase in both had the effect of improving QoL. We recommend developing strategies that increase PTG, and that mindfulness be performed to improve QoL among patients following liver transplantation.

Transplantology doi: 10.3390/transplantology6040035

Authors: Said A. Al-Busafi Mohammed Eslam

Metabolic dysfunction–associated fatty liver disease (MAFLD) is now the leading indication for liver transplantation (LT), reshaping the landscape of transplant hepatology. Its close association with obesity, type 2 diabetes, cardiovascular disease, and extrahepatic malignancies poses unique challenges throughout the transplant continuum. This narrative review synthesizes current evidence across the pre-, peri-, and post-transplant spectrum, with a focus on practical implications for clinical management. We explore pre-transplant evaluation, focusing on how metabolic comorbidities, frailty, and organ allocation disparities intersect with emerging interventions such as GLP-1 receptor agonists, bariatric surgery, and structured weight loss programs. The increase in pediatric MAFLD, especially its early-onset aggressive form, indicates an evolving and concerning future burden on transplant programs. In the peri-operative and post-transplant periods, we address MAFLD recurrence, cardiometabolic complications, and the rising incidence of new cancers, particularly in relation to calcineurin inhibitor (CNI) exposure. Customized immunosuppression strategies, using mTOR inhibitors and mycophenolate mofetil, are discussed for their role in balancing graft protection with reducing cancer risk. We also review the application of machine perfusion technologies to optimize and expand the pool of steatotic donor livers. Future directions include the development of non-invasive diagnostic biomarkers, precision immunosuppression, and genomics-based risk stratification. Collectively, these insights emphasize the urgent need for multidisciplinary, patient-specific approaches and prospective, multicenter studies to optimize outcomes and equity in the era of MAFLD-driven liver transplantation.

Transplantology doi: 10.3390/transplantology6040034

Authors: Vikash Chandra Mishra Dinesh Chandra Ritu Sharma Diksha Dhuliya Vimarsh Raina

Background/Objectives: Epitope-based matching has emerged as a refined approach for assessing donor–recipient compatibility in renal transplantation. However, limited data are available on HLA Class I epitope distribution among Indian patients, particularly from northern India, where substantial allelic diversity is known to influence immunological risk. Methods: This retrospective analysis evaluated HLA Class I single-antigen bead (SAB) antibody data from 218 consecutive renal-transplant candidates who tested positive for anti-HLA antibodies between July 2018 and September 2024. HLA Class I epitopes were identified and analyzed using MATCH IT Antibody Software (Immucor, version 1.5.0). Demographic variables and sensitization history (previous transplant, transfusion, pregnancy) were reviewed. Results: A total of 504 distinct epitopes were identified, with 65GK and 163LG emerging as the most frequent motifs. The predominance of these epitopes mirrors the high prevalence of alleles such as HLA-A*24 and HLA-B*35 reported in North-Indian populations. The data suggest a strong influence of regional allele architecture on the immunogenic epitope landscape. Conclusions: This study provides the first baseline characterization of HLA Class I epitope distribution among northern-Indian renal-transplant candidates. The findings emphasize the need for establishing population-specific HLA epitope databases and highlight the potential of epitope-based matching to enhance donor selection and minimize immunological risk in Indian transplantation programs.

Transplantology doi: 10.3390/transplantology6040033

Authors: Afrasyab Khan

Chronic kidney disease (CKD) remains one of the most frequent long-term complications following liver transplantation, with calcineurin inhibitor nephrotoxicity as an important and modifiable driver [...]

Transplantology doi: 10.3390/transplantology6040032

Authors: Hiba Ghabi Amira Khemiri Ikram Mami Syrine Tlili Jihen Sahli Fethi Ben Hmida Lamia Rais Mouhamed Karim Zouaghi

Background: Arterial stiffness assessed by measuring pulse wave velocity (PWV) is a well-established predictor of cardiovascular mortality. To our knowledge, no studies on arterial stiffness in kidney transplant recipients (KTRs) from Tunisia have been conducted. The present study aimed to assess arterial stiffness in Tunisian KTRs and to identify the key predictors associated with its increase. Methods: We conducted a cross-sectional, single-center study enrolling Tunisian KTRs aged 18 years or older with a minimum post-transplant follow-up of six months. Arterial stiffness was measured as pulse carotid–femoral PWV (CF-PWV) by a Complior device. A CF-PWV ≥ 10 m/s was defined as elevated. Results: Fifty-four KTRs were included (mean age: 42.55 ± 10.61 years). Among them, 19 (35.2%) had a CF-PWV ≥ 10 m/s. The univariate analysis showed a significant association between elevated CF-PWV and the following parameters: age, hypertension prior to transplantation, dyslipidemia, donor age, parameters obtained through office blood pressure measurement (systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP)), central SBP recorded by the Complior device, nocturnal SBP obtained through 24 h ambulatory blood pressure monitoring (ABPM), and fasting blood glucose. A multivariable analysis with CF-PWV ≥ 10 m/s as a dependent variable retained the following independent factors: dyslipidemia (p = 0.015; OR = 60.32), donor age (p = 0.014; OR = 1.16), SBP obtained through office blood pressure measurement (p = 0.015; OR = 1.25), and fasting blood glucose (p = 0.034; OR = 22.35). Conclusions: Given the major impact of cardiovascular disease on post-transplant outcomes, understanding the determinants of arterial stiffness is crucial for improving patient care. Routine PWV assessment may not be feasible in all centers due to cost or limited equipment availability. Therefore, identifying the clinical and biological markers associated with arterial stiffness offers a low-cost and widely accessible alternative for evaluating cardiovascular risk. These findings may support the development of a simple risk score to help nephrologists detect and manage high-risk KTRs more effectively.

Transplantology doi: 10.3390/transplantology6040031

Authors: Krysta Walter Alisia Chen Jennifer Hagopian Elizabeth Belloli Michael Combs Dennis Lyu Rommel Sagana

Background/Objectives: Calcineurin inhibitors (CNI) contribute to renal dysfunction post-transplant. Belatacept is a renal sparing immunosuppressive agent. We sought to determine if the use of belatacept, as an alternative to a CNI-based maintenance immunosuppressive regimen ameliorates the effects of CNI-related nephrotoxicity in lung transplant recipients, while preserving graft function. Methods: Retrospective case series of adult lung transplant recipients (LTR) converted to belatacept with CNI elimination between 2020 and 2023. Primary outcomes were estimated glomerular filtration rate (eGFR) and pulmonary function testing. Secondary outcomes included incidence of rejection, mortality, donor specific antibody (DSA), chronic lung allograft dysfunction, infection, malignancies, and drug discontinuation. Results: Five LTR converted to belatacept with a median follow up of 3.49 years (IQR 16.4). eGFR improved with a median change of +18 mL/min/1.73 m2 (IQR 6–34) at 12 months, this was sustained at last-follow-up (+19 mL/min/1.73 m2 (IQR 6–34)). Force expiratory volume in 1 s (FEV1) declined from baseline to last follow-up (median change −0.53 L). At a median of 199 days post-conversion (IQR 108–453), belatacept was discontinued in 4/5 (80%) LTR, primarily due to graft dysfunction (3/4), and CNI therapy resumed. No LTR developed CLAD, DSA, malignancy, or died on belatacept. Infection (primarily pulmonary bacterial or fungal) occurred in all LTR on belatacept. Conclusions: Belatacept with complete CNI elimination in LTR resulted in a sustained improvement in renal function in this series but was accompanied by a high discontinuation rate due to worsening graft function. The risks to the graft associated with belatacept and calcineurin inhibitor elimination outweigh any potential renal benefits.

Transplantology doi: 10.3390/transplantology6040030

Authors: Rachel B. Allen Emily Stevenson April L. Goley Bonnie Alexander Joanna Ma Taylor B. Raiger Mary M. Chandran Kristen R. Szempruch

Background: Post-transplant diabetes mellitus (PTDM) is a complication of kidney transplantation, but the impact of early hyperglycemia (EH) remains unclear. This study aimed to assess the incidence of PTDM in kidney transplant recipients (KTRs) who experienced EH compared to those who do not at 6 months post-transplant. Methods: A single-center, retrospective cohort study was conducted in adults who underwent kidney transplantation from 1 January 2019 to 25 May 2022. KTRs who developed EH were compared against those who did not. Results: The primary outcome was the difference in incidence of PTDM at 6 months. Secondary outcomes included rehospitalizations and infections within 6 months and PTDM, renal function, cardiovascular events, and graft and patient survival within 12 months. Two hundred and seventy-nine KTRs (EH, n = 204 vs. comparator, n = 75) were included. There were higher incidences of PTDM in the EH group compared to the comparator group at 6 months (11% vs. 1.4%, p = 0.012) and 12 months post-transplant (18.5% vs. 5.5%, p = 0.007). KTRs with EH had 8.9 times greater odds of developing PTDM (OR 8.9; 95% 1.2–67.3, p = 0.03) at 6 months. There was no significant difference found in other secondary outcomes. Conclusions: KTRs with EH had an increased incidence of developing PTDM.

Transplantology doi: 10.3390/transplantology6040029

Authors: Lubov Korneva Yulia Sazonova Maria Bortsova Maria Simonenko Georgii Baratashvili Olga Kalinina Ekaterina Zaikova Darina Sambur Alexey Golovkin Petr Fedotov

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.

Transplantology doi: 10.3390/transplantology6030028

Authors: Chiara Catelli Andrea Lloret Madrid David Bennett Miriana D’Alessandro Marco Guerrieri Marianna Rizzo Daniele Marianello Antonella Fossi Piero Paladini Elena Bargagli Luca Luzzi

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.

Transplantology doi: 10.3390/transplantology6030027

Authors: Talal Al-Qaoud Rawan Al-Yousef Basma Behbehani Abdullatif Al-Terki

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.

Transplantology doi: 10.3390/transplantology6030026

Authors: Chloe Ballesté Seow-Huey Choy Mauricio Galvao Brian Alvarez Carmen Blanco Joaquim Albiol Patricia Peralta David Paredes Martí Manyalich Ricard Valero

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.

Transplantology doi: 10.3390/transplantology6030025

Authors: Thuy-Duyen Nguyen Dora Lam-Himlin Blanca Lizaola-Mayo David Chascsa

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.

Transplantology doi: 10.3390/transplantology6030024

Authors: Reza Rahimi Shahmirzadi Danielle Ouellette Martin Igbokwe Alp Sener Manal Y. Gabril Subrata Chakrabarti Uday Deotare Lili Ataie

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.

Transplantology doi: 10.3390/transplantology6030023

Authors: Kavyesh Vivek Vassilios Papalois

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.

Transplantology doi: 10.3390/transplantology6030022

Authors: Lorenzo Giovannico Valeria Ladisa Simona De Santis Giuseppe Fischetti Domenico Parigino Luca Savino Federica Mazzone Nicola Di Bari Massimo Padalino Tomaso Bottio

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.

Transplantology doi: 10.3390/transplantology6030021

Authors: Kevin Verhoeff Uzair Jogiat Alessandro Parente Blaire Anderson Khaled Dajani David L. Bigam A. M. James Shapiro

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.

Transplantology doi: 10.3390/transplantology6030020

Authors: Lucas Gartzke Julia Huisman Nora Spraakman Fernanda Lira Chavez Michel Struys Henri Leuvenink Robert Henning Gertrude Nieuwenhuijs-Moeke

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.

Transplantology doi: 10.3390/transplantology6020019

Authors: Ritika Mazumder Andrew Ford Omar T. Sims Jamak Modaresi Esfeh

In the original publication [...]

Transplantology doi: 10.3390/transplantology6020018

Authors: Katrina Tan Karl Vaz Sophie Testro Khashayar Asadi Adam Testro

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.

Transplantology doi: 10.3390/transplantology6020017

Authors: Maria Keller Megumi Inoue Naoru Koizumi Samantha Meyo Anne Solbu Matthew Handmacher Liise Kayler

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.

Transplantology doi: 10.3390/transplantology6020016

Authors: Jenna N. Whitrock Michela M. Carter Adam D. Price Aaron M. Delman Catherine G. Pratt Jiang Wang Divya Sharma Ralph C. Quillin Shimul A. Shah

In the original publication [...]

Transplantology doi: 10.3390/transplantology6020015

Authors: Tancredi Vincenzo Li Cavoli Armando Curto Erica Nicola Lynch Andrea Galli

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.

Transplantology doi: 10.3390/transplantology6020014

Authors: Maurizio Salvadori Giuseppina Rosso

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.

Transplantology doi: 10.3390/transplantology6020013

Authors: Zuleyha Simsek Yaban Semra Bulbuloglu

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.

Transplantology doi: 10.3390/transplantology6020012

Authors: Filomena Emanuela Laddaga Pierluigi Masciopinto Valentina Bozzoli Domenico Pastore Vincenzo Pavone Angelo Michele Carella Nicola Di Renzo Attilio Guarini Pellegrino Musto Francesco Gaudio

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.

Transplantology doi: 10.3390/transplantology6020011

Authors: Albert Dweck Korri S. Hershenhouse Mayuko Uehara Tadahisa Sugiura Brandon E. Ferrell

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.

Transplantology doi: 10.3390/transplantology6020010

Authors: E. A. J. Alkemade H. D. Lam B. J. C. Hendriks A. E. Braat I. P. J. Alwayn M. J. Coenraad A. G. Baranski

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.

Transplantology doi: 10.3390/transplantology6020009

Authors: Vikash Chandra Mishra Dinesh Chandra Vimarsh Raina

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.

Transplantology doi: 10.3390/transplantology6020008

Authors: Dafni Efraimoglou L. Annick van Furth Albert Gerding Barbara M. Bakker Jan-Luuk Hillebrands Henri G. D. Leuvenink Leonie H. Venema

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.

Transplantology doi: 10.3390/transplantology6010007

Authors: Yoon-Jung Chang Samuel Simpson Megan Charette Obi Ekwenna

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.

Transplantology doi: 10.3390/transplantology6010006

Authors: Desmond Offei Dulat Bekbolsynov Stanislaw Stepkowski Robert Green

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.

Transplantology doi: 10.3390/transplantology6010005

Authors: Vasco Quaresma Margarida Carneiro Lorenzo Marconi Edgar Tavares da Silva Roberto Jarimba Miguel Eliseu Pedro Nunes Arnaldo Figueiredo

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.

Transplantology doi: 10.3390/transplantology6010004

Authors: Le Xuan Cung Luong Thi Anh Thu Duong Mai Nga Pham Ngoc Dong

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.

Transplantology doi: 10.3390/transplantology6010003

Authors: Kevin Lor Catherine Le Evan Kransdorf Michelle Kittleson

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.

Transplantology doi: 10.3390/transplantology6010002

Authors: Sebastian Wolf Stefan Schiele Matthias Schrempf Florian Sommer Mingming Li Ulrich Wirth Jens Werner Joachim Andrassy

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.

Transplantology doi: 10.3390/transplantology6010001

Authors: Alessandra Agnese Grossi

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.

Transplantology doi: 10.3390/transplantology5040031

Authors: Thang Diep Tam Thai Thanh Tran Chuan Khac Hoang Sam Minh Thai

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.

Transplantology doi: 10.3390/transplantology5040030

Authors: Decheng Yin Oliver Dewald Xiangyu Peng Wenlong Nie Song Rong Diana Dudziak Christian H. K. Lehmann André Hoerning Jian Fu

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.

Transplantology doi: 10.3390/transplantology5040029

Authors: Lovepreet Singh Ramanpreet Bajwa Sofia Molina Garcia Kristelle Imperio-Lagabon Omar T. Sims Jamak Modaresi Esfeh

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.

Transplantology doi: 10.3390/transplantology5040028

Authors: Molly E. Casey Emmalie Yanacek Hitesh Kaul John P. Knorr Kamran Khanmoradi Afshin Parsikia Nikolaos Chandolias Kevin K. Zarrabi Radi Zaki

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.

Transplantology doi: 10.3390/transplantology5040027

Authors: Badi Rawashdeh Joohyun Kim Ty Dunn Haneen Al-Abdallat Ahmad Qasem Rootvij Bhatt Raj Prasad Matthew Cooper

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.

Transplantology doi: 10.3390/transplantology5040026

Authors: Octavio Herrera Alexis Garza Maria Veronica Rodriguez Manuel De Jesus-Escano Samuel Serna Jose Almeda Gaudencio Olgin

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.

Transplantology doi: 10.3390/transplantology5040025

Authors: Piyush Kumar Sinha Kishore GS Bharathy

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.

Transplantology doi: 10.3390/transplantology5040024

Authors: Tenzin Yongye Maria Keller Surjo Bandyopadhyay Ahmad Zaaroura Liise K. Kayler

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.

Transplantology doi: 10.3390/transplantology5040023

Authors: Tristan Meier Kathryn Schmidt Kristin Cole Jody C. Olson Timucin Taner Douglas A. Simonetto Samy Riad

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.

Transplantology doi: 10.3390/transplantology5030022

Authors: Maurizio Salvadori Alberto Rosati Giuseppina Rosso

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.

Transplantology doi: 10.3390/transplantology5030021

Authors: Ayusha Poudel Anurag Adhikari Sajana Poudel Aayush Poudel

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.

Transplantology doi: 10.3390/transplantology5030020

Authors: Saif Yamin Hamzeh Feras Alshahwan Jehad Feras AlSamhori Osama Alfreahat Abdallah Alhalbouni Zaid Alwarawrah

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.

Transplantology doi: 10.3390/transplantology5030019

Authors: Patricia Mae De Leon Heherson Cabrera

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.

Transplantology doi: 10.3390/transplantology5030018

Authors: Ritika Mazumder Andrew Ford Omar T. Sims Jamak Modaresi Esfeh

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.

Transplantology doi: 10.3390/transplantology5030017

Authors: Todd J. Robinson Thierry Schöb Paola A. Vargas Caroline Schöb Alp Demirag Jose Oberholzer

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.

Transplantology doi: 10.3390/transplantology5030016

Authors: Aleksandra Maciejczyk Anna Łabuś Mariusz Niemczyk

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.

Transplantology doi: 10.3390/transplantology5030015

Authors: Caitlin M. Blades Nalu Navarro-Alvarez Christene A. Huang David W. Mathes

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.

Transplantology doi: 10.3390/transplantology5030014

Authors: Mohammad Ammad Ud Din Qurratul Ain Muhammad Shan Ul Abedin Moazzam Shahzad Muhammad Umair Mushtaq

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.

Transplantology doi: 10.3390/transplantology5030013

Authors: Alberto Ferrarese Marco Senzolo Anna Maria Cattelan Lolita Sasset Sara Battistella Alberto Zanetto Giacomo Germani Francesco Paolo Russo Martina Gambato Filippo Pelizzaro Stefania Vio Domenico Bassi Umberto Cillo Patrizia Burra

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.

Transplantology doi: 10.3390/transplantology5030012

Authors: Maurizio Salvadori Alberto Rosati Giuseppina Rosso

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.

Transplantology doi: 10.3390/transplantology5020011

Authors: Ji Ae Yoon Cherng Chao Zurabi Lominadze

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.

Transplantology doi: 10.3390/transplantology5020010

Authors: John Guzzi Eric Strand Burhan Ozturk Daniel Agarkov Ranjit Deshpande

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.

Transplantology doi: 10.3390/transplantology5020009

Authors: Vikash Chandra Mishra Dinesh Chandra Vimarsh Raina

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.

Transplantology doi: 10.3390/transplantology5020008

Authors: Marco Di Pangrazio Federico Pinto Alessandro Martinino Francesco Toti Gioia Pozza Francesco Giovinazzo

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.

Transplantology doi: 10.3390/transplantology5020007

Authors: Samuel Mangold Gergely Albu Julien Maillard Florence Aldenkortt Eduardo Schiffer

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.

Transplantology doi: 10.3390/transplantology5020006

Authors: Ceilidh McKenney Julia Torabi Rachel Todd M. Zeeshan Akhtar Fasika M. Tedla Ron Shapiro Sander S. Florman Matthew L. Holzner L. Leonie van Leeuwen

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.

Transplantology doi: 10.3390/transplantology5010005

Authors: Jenna Whitrock Michela Carter Adam Price Aaron Delman Catherine Pratt Jiang Wang Divya Sharma Ralph Quillin Shimul Shah

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.

Transplantology doi: 10.3390/transplantology5010004

Authors: Antonio Franco Esteve Patricio Mas-Serrano Fransico Manuel Marco Eduardo Garin Cascales Francisco Javier Perez Contreras

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.

Transplantology doi: 10.3390/transplantology5010003

Authors: Kathleen O’Neill Elliott G. Richards Jessica Walter Sharon West Richard Hasz Giuliano Testa Shreya Kalra Tommaso Falcone Rebecca Flyckt Nawar Latif Andreas Tzakis Liza Johannesson

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.

Transplantology doi: 10.3390/transplantology5010002

Authors: Brian Carter Laveen Khoshnaw Megan Simmons Lisa Hines Brandon Wolfe Mitchell Liester

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.

Transplantology doi: 10.3390/transplantology5010001

Authors: René Hage Macé Matthew Schuurmans

Introduction: Frailty is a complex pathobiological process characterized by diminished physiological reserve and increased vulnerability to stressors, which has been associated with unfavorable outcomes before and after lung transplantation. Methods: We undertook an extensive narrative review, encompassing a thorough exploration of original papers, observational studies, case reports, and meta-analyses published between 1990 and July 2023, in various databases, including PubMed, Embase, Cochrane Library, Wiley Online Library databases, and Google Scholar. The search terms [frailty] AND [lung transplant] were utilized. Additionally, the reference lists of retrieved articles were examined. Inclusion criteria comprised studies written in English and involving human subjects. The identified studies were categorized into pre-transplant and post-transplant populations, and the measurement tools used to assess frailty were analyzed, along with the clinical implications reported in the studies. Results: From 1 January 1990 to 1 July 2023, a total of 10 studies on frailty and lung transplantation were identified through online sources and bibliographic searches, involving a total of 2759 patients. Among these studies, six focused on the pre-transplant population, while four examined the post-transplant population. The Fried Frailty Phenotype (FFP) and the Short Physical Performance Battery (SPPB) were the most employed tools for measuring frailty. A table presents additional frailty assessment instruments and the clinical implications described in the studies. Conclusions: Frailty is prevalent both in patients with end-stage respiratory diseases awaiting lung transplantation and in postoperative lung transplant recipients. Most transplant centers recognize the value of assessing frailty in the evaluation of potential candidates for lung transplantation. Frailty has been shown to impact mortality on the waitlist and in the post-transplant period. However, the most effective methods for measuring frailty in lung transplant candidates and recipients have yet to be determined. Strategies to reverse frailty are available and show promising results on outcomes.

Transplantology doi: 10.3390/transplantology4040022

Authors: Max Levine Patrick Luke Alp Sener Heather Resvick Stephanie Braga Taralynn St. Kitts Sarah De Marinis Janet Madill

Background: Quadriceps muscle layer thickness (QMLT), which is measured using ultrasound, is an emerging strategy to identify sarcopenia. Purpose: The purpose of the study was to assess whether pre-operative QMLT values are associated with a prolonged length of stay (LOS; defined as >14 days) following a renal transplant. Methods: Between March 2019 and January 2020, we performed a prospective study among patients undergoing renal transplantation. Physical Frailty scores and QMLT measurements were performed pre-operatively. The primary outcome was a greater LOS following transplant. Secondary outcomes included complications and renal function. Statistical analysis: Percentiles divided patients into two categories of QMLT (low and high). Continuous outcomes were compared using a two-sided t-test or Mann–Whitney U test, and Chi-square analysis and Fisher exact testing were used for nominal variables. Results: Of 79 patients, the frailty prevalence was 16%. Among patients with low and higher QMLTs, LOS of >14 days were 21% vs. 3% [p = 0.04], respectively. Demographically, there was a higher percentage of patients with living donors in the high- vs. low-QMLT groups (40 vs. 7%). However, in a subgroup analysis excluding living-donor recipients, the difference between groups was preserved (23% vs. 0%, p = 0.01). No differences in secondary outcomes were seen between groups. Conclusions: Low quadriceps muscle layer thickness may be associated with a prolonged length of stay for renal recipients. Further research is needed to confirm our findings.

Transplantology doi: 10.3390/transplantology4040021

Authors: Sabrina Congedi Annalisa Boscolo Marco Nardelli Martina Biscaro Christian Legnaro Nicolò Sella Giulia Fichera Tommaso Antonio Giacon Paola Zanon Davide Lovison Mara Bassi Bianca Maria Borrelli Giulia Lorenzoni Chiara Giraudo Dario Gregori Federico Rea Paolo Navalesi

Background: Scant data are available on nutritional status in bilateral lung transplant (BLT) candidates. Methods: All consecutive recipients admitted to the intensive care unit (ICU) of the University Hospital of Padua (February 2016–2020) after bilateral-lung transplant (BLT) were retrospectively screened. Data collected: (i) nutritional indices (body mass index (BMI), albumin level, prognostic nutritional index (PNI), mini nutritional assessment short-form (MNA-SF)); and (ii) muscular indices (creatinine height index (CHI)), skeletal muscle index (SMI), densitometry of paravertebral muscles on chest CT). Results: 108 BLT recipients were enrolled: 55% had a normal BMI, 83% had serum albumin levels > 35 g/L; high PNI and MNA-SF scores were recorded in most of patients. A total of 74% had a “normal or slightly reduced protein state“ according to the CHI score; 17% were identified as “sarcopenic” according to muscle densitometry (Hu < 30). Lower serum albumin was associated with longer invasive mechanical ventilation days (IMV) and ICU length of stay (p-value for non-linearity < 0.01). PNI and BMI were also associated with an increased ICU length of stay (p-value for non-linearity < 0.01). Conclusions: Most of the BLT recipients had normal nutritional and sarcopenia status. Pre-transplant albumin values correlated with the duration of IMV; serum albumin, PNI and BMI were associated with ICU stay. No nutritional or muscle parameters predicted re-intubation, 30-days rejection and overall length of hospital stay.

Transplantology doi: 10.3390/transplantology4040020

Authors: Bibhuti Das Justin Godown Shriprasad R. Deshpande

Objectives: Limited data are available on renal dysfunction and neurologic complications in heart failure in children, when the heart failure is not related to congenital heart disease (CHD) or cardiac surgery. This study used a multi-center database to describe pediatric heart failure (pHF)-related renal dysfunction, neurological complications, and outcomes in non-CHD patients. Methods: The Pediatric Health Information System (PHIS) database between 2004 and 2020 was used to analyze the prevalence of renal dysfunction and neurologic complications associated with pHF hospitalizations and their impact on outcomes. Results: Of the 5515 hospitalizations included in the study, renal dysfunction was identified in 1239 (22.5%), and neurologic dysfunction was diagnosed in 539 (9.8%). The diagnosis of renal or neurologic complications was associated with significantly higher use of ICU therapies, including mechanical ventilation, parenteral nutrition, and mechanical circulatory support. Patients with significant renal dysfunction were likely to receive kidney transplants in 3.1% of the cases. Neurologic complications were higher in patients with pHF who underwent heart transplantation (21.3% vs. 7.8%, p < 0.001). Patients with renal dysfunction and neurologic complications had significantly higher mortality rates than those without renal dysfunction (11.7% vs. 4.3%, p < 0.001) and neurologic complications (18.4% vs. 4.6%, p < 0.001). Conclusions: Renal dysfunction and neurologic complications are common, resulting in significantly higher utilization of ICU therapies and mortality rates during non-CHD-related pHF hospitalization. Neurologic complications associated with hospitalization for pHF are associated with a significantly higher mortality, which has been underemphasized in the literature. This study assesses the burden of these morbidities and highlights the importance of monitoring and managing renal and neurologic complications in pHF to improve outcomes.

Transplantology doi: 10.3390/transplantology4040019

Authors: Jane Y. Zhao Doug A. Gouchoe William E. Schwartzman Justin P. Rosenheck Victor Heh Matthew C. Henn Nahush A. Mokadam David R. Nunley Bryan A. Whitson Asvin M. Ganapathi

A retrospective review of the UNOS/OPTN Database was performed from 1 October 1987–31 December 2019. Recipients were classified as LSu (15+ years survival without GF/ReTx), normal survival (3–15 years) and short survival (<3 years). In total, 22,646 patients were identified. Groups were assessed with comparative statistics in addition to a multivariate analysis which included recipient, donor, transplant characteristics and select post-transplant complications. LSu recipients were younger, more commonly female, healthier and more commonly had cystic fibrosis, pulmonary vascular disease or bilateral lung transplantation. LSu donors were younger, healthier and lacked clinical infection. Recipients with restrictive lung disease, single lung transplant and dialysis postoperatively were less likely to be LSu. Several recipient, donor and transplant characteristics are associated with long lung transplantation survival. While some factors cannot be altered, others related to donor selection and posttransplant management can potentially be influenced. Understanding these characteristics and employing discretion in donor selection, in appropriate recipients, may optimize the longevity of transplanted lungs.

Transplantology doi: 10.3390/transplantology4040018

Authors: Carmen A. Moes C. Tji Gan Leonie H. Venema Roland F. Hoffmann Barbro N. Melgert Huib A. M. Kerstjens Peter Olinga Mitchel J. R. Ruigrok

Background: Donor lungs are often discarded, with gastric aspiration accounting for ~9% of lungs unsuitable for transplantation. To increase the donor pool, it is important to understand the pathophysiology of aspiration-induced lung damage (AILD) and to assess its treatment. Methods: Precision-cut lung slices (PCLS) were prepared from murine lungs and exposed to acid—pH 1.5 to 5.5—for 15 min. We also investigated whether acid-exposed slices (pH 3.5) could affect unexposed slices. In addition, we investigated whether dexamethasone (0.5 or 1 μM) could mitigate and treat the damage in each group. In each experiment (n = 3), we analyzed cell viability (ATP/protein content) and markers of inflammation (IL-1β, IL-6, TNF-𝛼, TRAIL). Results: PCLS subjected to pH 1.5–3.5 had a significantly reduced amount of ATP, albeit no increase in inflammation markers. There was no interaction of secretions from acid-exposed slices on unexposed slices. Dexamethasone had no beneficial effects in either group. Conclusion: Direct exposure to acid in the PCLS leads to a decrease in cell viability. Acid-exposed slices had no effect on the cell viability of unexposed slices. Treatment with dexamethasone offered no mitigation. More studies have to be performed to elucidate the pathophysiology of AILD and the possible treatment of aspiration-induced injury.

Transplantology doi: 10.3390/transplantology4030017

Authors: Jes M. Sanders Daniel Galvez Xiaoqi Lin Joseph Leventhal

Splenosis is a benign, acquired condition characterized by the auto-implantation of focal deposits of splenic tissue throughout the peritoneal cavity, most commonly occurring after splenic injury and/or splenectomy. Post-Transplant Lymphoproliferative Disorder (PTLD) is a well-known complication of solid organ transplantation that results from unregulated B-cell proliferation due to chronic immunosuppression. Given their clinical and radiologic similarities, these two entities may pose a diagnostic dilemma in select solid-organ transplant recipients. We present the case of a 54-year-old kidney-transplant recipient presenting with abdominal pain and found to have a retroperitoneal soft-tissue mass concerning for PTLD. He underwent a CT-guided biopsy of the mass, and histopathological studies revealed lymphoid tissue consistent with splenic tissue, thus ruling out PTLD. The patient subsequently underwent symptomatic management, with the eventual resolution of his symptoms. The early diagnosis of PTLD is paramount, as prompt intervention has a substantial impact on the high rate of morbidity and mortality associated with this condition. Additionally, the diagnosis of splenosis in the setting of a retroperitoneal mass is critical in order to avoid invasive diagnostic and therapeutic procedures that may result in significant complications. A detailed surgical history, including prior splenic trauma and/or splenectomy, should raise clinical suspicion for splenosis and guide further diagnostic and therapeutic decision making.

Transplantology doi: 10.3390/transplantology4030016

Authors: Hwarang S. Han Michelle L. Lubetzky Nidharshan S. Anandasivam Rebecca A. Cox Brian K. Lee

Immunoglobulin A nephropathy (IgAN) is the commonest glomerulonephritis worldwide, a category that represents the third most frequent cause of end-stage kidney disease (ESKD) in the United States. Kidney transplantation remains the optimal treatment of ESKD, and yet the prospects of IgAN recurrence post-transplant dampens the enthusiasm for living kidney donation in some instances, in addition to limiting the longevity of the kidney allograft. Moreover, the lack of a standardized method for detecting IgAN recurrence, since not all centers perform protocol allograft biopsies, has led to an underestimation of the extent of the issue. The pathogenesis of de novo IgAN remains conjectural, let alone the pathways for recurrent disease, but is increasingly recognized as a multi-hit injury mechanism. Identification of recurrent disease rests mainly on clinical symptoms and signs (e.g., hematuria, proteinuria) and could only be definitively proven with histologic evidence which is invasive and prone to sampling error. Treatment had relied mainly on nonspecific goals of proteinuria reduction, and in some cases, immunosuppression for active, crescentic disease. More recently, newer targets have the potential to widen the armamentarium for directed therapies, with more studies on the horizon. This review article provides an update on recurrent IgAN post-transplant.

Transplantology doi: 10.3390/transplantology4030015

Authors: Damiano Patrono Ana Lavinia Apostu Giorgia Rizza Davide Cussa Antonella Barreca Selene Limoncelli Stefano Mirabella Renato Romagnoli

Graft steatosis has been associated with inferior outcomes after liver transplantation. Given the rising prevalence of obesity and fatty liver disease, strategies allowing safe and successful utilization of fatty liver grafts are needed. Liver preservation by normothermic machine perfusion (NMP) allows reducing ischemia-reperfusion injury, extending preservation time and assessing graft viability prior to implantation into the recipient. NMP can be initiated at the donor hospital using a transportable device (referred to as upfront NMP or normothermic machine preservation) or after a period of cold ischemia (known as back-to-base). In this report, we present the case of a graft from an HCV-positive DBD donor with 70% macrovesicular steatosis, which was successfully preserved and transplanted using upfront NMP. This approach was key to minimize initial injury to the graft and allowed assessing its viability before transplantation, while improving transplant logistics. Upfront NMP represents a promising approach to enhance the transplantation of fatty liver grafts.

Transplantology doi: 10.3390/transplantology4030014

Authors: Maurizio Salvadori

The presence in a recipient of antibodies directed against donor-specific antigens represents a major obstacle to transplantation. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques, and old and new drugs are currently used for desensitizing these patients. Desensitization may either occur before transplantation, at the time of transplantation, or after transplantation according to whether physicians are dealing with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivities and specificities, and different advantages and drawbacks. The targets of the drugs used to desensitize are B cells, plasma cells, the antibodies themselves, and, finally, the complement that is the final actor causing tissue disruption. B cells are relatively easy to target; targeting the plasma cell is more difficult. Indeed, several new drugs are also used in randomized trials to defeat plasma cells. Antibodies may be removed easily, but their removal is often followed by antibody rebound. The complement is not easy to defeat and new drugs are currently used for this aim. Overall, despite difficulties, desensitization is currently possible in many cases, to obtain a safe and successful transplantation.

Transplantology doi: 10.3390/transplantology4030013

Authors: Corey Mealer Haley Konsek Zachary Travis Rebecca N. Suk Taufiek Konrad Rajab

Cold preservation is a key component to organ procurement and transplantation. Cold preservation functions by slowing metabolic activity of procured organs and begins the period known as cold ischemic time (CIT). Reducing CIT and warm ischemic time (WIT) are paramount to minimizing donor organ damage from ischemia and the build-up of waste products and signals that drive reperfusion injury prior to transplantation into a matching recipient. Preventing damage from CIT and WIT and extending the amount of time that organs can tolerate has been a major goal of organ transplantation since donors and recipients are frequently not located within the same hospital, region, or state. Meanwhile, the amount of CIT that a transplant center is willing to accept differs based on the organ, the institution receiving the organ offer, and the doctor receiving the offer for that institution. With the introduction of a partial heart transplantation conducted last year at Duke University, it is important to discuss how much CIT transplant centers conducting a partial heart transplantation (pHT) are willing to accept. This article will review the physiology of WIT and CIT, associated organ damage, CIT variation among transplant centers and organ types, and provide a brief discussion of the future of pHT-accepted CIT and the need for research in this field.

Transplantology doi: 10.3390/transplantology4030012

Authors: Luis Carlos Alvarez-Perdomo John Ubeimar Cataño-Bedoya Maribel Plaza-Tenorio Ana María Botero-Mora Isabel del Pilar Cardozo-Moreno Luis Manuel Barrera-Lozano Jaime Alberto Ramírez-Arbeláez Carlos M. Ardila

The purpose of the study was to characterize lower extremity peripheral arterial disease (LEPAD) in a series of kidney transplant patients and to assess the impact on adverse outcomes. A retrospective cohort study was conducted including kidney transplant recipient patients who underwent screening for LEPAD. The outcomes evaluated were classified as perioperative and post-transplant, including cardiovascular events, amputation, mortality, and loss of the graft. A total of 141 renal transplant patients screened for LEPAD were identified, with an average follow-up of 3 years. LEPAD occurred in 14.2% (20/141). No differences in cardiovascular risk factors were found between the groups, except for smoking (45% vs. 24%, p < 0.05). In the group with LEPAD, the most compromised anatomical segment was the infrapopliteus, with no iliac involvement found. The Cox proportional hazards model indicated that the variables age, gender, and weight were significant in patients with LEPAD. There were no differences between the groups in terms of graft loss and death. The infrapopliteal segment is the area of greatest stenosis in kidney transplant patients with LEPAD. Together with smoking, they can explain the presence of major amputations in kidney transplant patients; however, they had no impact on graft functionality or death.

Transplantology doi: 10.3390/transplantology4030011

Authors: Silvia Aguado Ibáñez Rosalía Laporta Hernández Myriam Aguilar Pérez Christian García Fadul Cristina López García Gallo Gema Díaz Nuevo Sonia Salinas Castillo Raquel Castejón Diaz Clara Salas Anton Ana Royuela Vicente Francisco Antonio Bernabeu Andreu María Piedad Ussetti Gil

The usefulness of bronchoalveolar lavage fluid (BALF) to support the diagnosis of acute cellular (ACR) rejection in lung transplant (LTX) recipients remains controversial. ACR has been associated with blood eosinophil counts (EOS) in other solid organ recipients, but there are few studies in relation to lung transplants. Our aim was to assess the usefulness of the combined analysis of BALF cellularity and EOS for the diagnosis of ACR in lung transplant recipients. This is a retrospective study of findings observed simultaneously in 887 transbronchial biopsies (TBB), BALF, and blood samples obtained from 363 LTx patients transplanted between 2014 and 2020. The variables collected were: demographics, ACR degree, BALF cellularity, and simultaneous blood EOS counts. The lymphocyte count in BALF was significantly higher in patients with ACR than in those without (11.35% vs. 6.11%; p < 0.001). In parallel, EOS counts were also significantly higher in patients with ACR than in the non-ACR group (EOS 213 ± 206/mm3 vs. 83 ± 129/mm3; p < 0.001). Increases in both parameters were associated with an increased risk of ACR (lymphocytes OR 1.100; 95% CI 1.080–1.131; EOS OR 1.460; 95% CI 1.350–1.580). The diagnostic specificity of ACR for a lymphocyte count > 12% was 71.1%, which increased to 95.8% when taking into account a simultaneous blood EOS count > 200/mm3. Simultaneous assessment of BALF lymphocyte counts and blood eosinophil counts may be useful for diagnosing ACR in patients with risk factors for TBB or in the presence of inconclusive histological samples.

Transplantology doi: 10.3390/transplantology4020010

Authors: Sandro Hügli Philip C. Müller Matthias Pfister Fabian Rössler

Background: Despite great progress in graft survival and complication rates, pronounced inflammatory responses are common after pancreas transplantation (PT). Subsequent to the first postoperative increase in inflammatory markers, we have frequently observed a second peak of C-reactive protein (CRP) and white blood cells (WBCs) following PT. This analysis is to assess the incidence and clinical relevance of late-onset increases in inflammatory markers following PT. Materials and methods: We analyzed all consecutive PTs over a 20-year period. The second peak of CRP (SCP) and WBCs (SWP) was defined as an increase >3 days after PT subsequent to a relevant initial decrease. Results: Of 116 patients, 60 (51.7%) developed SCP. SCP was not associated with pancreas graft loss or with thrombosis at discharge or at 90 days after PT (6.7% vs. 0.0%, p = 0.1; 8.3% vs. 1.8%, p = 0.2; and 15.0% vs. 3.6%, p = 0.06, respectively). Patients with SCP had more complications overall at discharge and at 90 days (85.0% vs. 50.0%, p < 0.001 and 93.3% vs. 76.8%, p = 0.02). In multivariable analysis, SCP was significantly associated with pre-transplant HbA1c (OR 2.1 (95% CI: 1.3–3.8); p = 0.005) and female gender (OR 0.03 (95% CI: 0.004–0.14); p ≤ 0.001). No significant association was found between SCP and pancreas cold ischemia time (OR 1.0 (95% CI: 1.0–1.0); p = 0.1), donor age (OR 1.01 (95% CI: 0.96–1.06); p = 0.7), recipient age (OR 0.9 (95% CI: 0.9–1.0); p = 0.1), or recipient BMI (OR 0.9 (95% CI: 0.9–1.4); p = 0.3). SWP did not differ in patients with or without SCP (p = 0.07) and there was no correlation with pancreas graft loss or relaparotomy (p = 0.3 and p = 0.6, respectively). Insulin-free graft survival after 1, 5, and 10 years did not differ between patients with SCP and those without SCP (95.0%, 90.2%, 90.2% vs. 96.1%, 91.2%, 88.7%, respectively; p = 0.964). Conclusion: Late-onset inflammatory reactions are frequently seen in PT and are correlated with higher overall complication rates. They are not correlated, however, with graft-specific complications or insulin-free graft survival.

Transplantology doi: 10.3390/transplantology4020009

Authors: Maurizio Salvadori

One of the major challenges in developing programs for kidney transplantation is represented by the presence of antibodies targeting the HLA of the donor in the recipients and, in particular cases, the incompatibility of the ABO blood groups among donor and recipient for living donors [...]

Transplantology doi: 10.3390/transplantology4020008

Authors: Pasquale Auricchio Michele Finotti

Chronic liver injury and subsequent liver fibrosis are usually a slow process without any specific or no clinical signs, resulting in pathological conditions with a poor chance of improvement through medical and surgical treatment, which if not promptly recognized, often lead to a liver transplant as the only therapeutic option. On the other hand, screening and follow-up are hard to establish in large populations using regularly invasive methods such as biopsies and other expensive diagnostic tools due to cost and a lack of adequate specificity and sensibility. In the last few years, a large variety of serological and radiological tests have been proposed to assess liver fibrosis. In this review, we will consider the most commonly used scores to evaluate liver fibrosis, with a special focus on the NAFLD pathogenesis. We will try to answer the question: can we rely on them?

Transplantology doi: 10.3390/transplantology4020007

Authors: L. Leonie van Leeuwen Mitchel J. R. Ruigrok Henri G. D. Leuvenink Peter Olinga

Circulatory death donor (DCD) kidneys are increasingly used to enlarge the donor pool. These kidneys undergo ischemia-reperfusion injury, frequently leading to renal fibrosis. Transforming growth factor beta 1 (TGF-β1) and matrix metalloproteases have been identified as central mediators of fibrosis and inhibition of these targets could attenuate fibrosis. We studied whether galunisertib, doxycycline, taurine, and febuxostat alleviated fibrosis in precision-cut kidney slices (PCKS). PCKS were prepared from porcine kidneys that were exposed to 30 min of warm ischemia followed by 3 h of oxygenated hypothermic machine perfusion. We subsequently incubated PCKS for 48 h at 37 °C with the described compounds. To further elucidate the antifibrotic effects of galunisertib, we cultured PCKS with TGF-β1. We first screened the effects of the compounds without TGF-β1. Most significant effects were observed for galunisertib which lowered the expression of ACTA2, TGFB1, FN2, and SERPINE1. We then investigated the effects of galunisertib in fibrotic PCKS incubated with TGF-β1. TGF-β1 significantly increased expression of TGFB1, FN1, SERPINE1, and SERPINH1. Galunisertib, however, attenuated the expression of all fibrosis-related genes. Galunisertib appears to be a promising antifibrotic compound requiring further research in a preclinical model and may ultimately be administered during machine perfusion as an antifibrotic treatment in a transplant setting.

Transplantology doi: 10.3390/transplantology4020006

Authors: Kishore GS Bharathy Sunil Shenvi

Background: When a partial liver graft is transplanted into a recipient with portal hypertension, it is subject to sinusoidal shear stress, which, in good measure, is essential for regeneration. However, portal hyperperfusion which exceeds the capacity of the graft results in the small-for-size syndrome manifested by ascites, cholestasis and coagulopathy. This review discusses intraoperative hemodynamic variables that have been described in the literature, and inflow modulation strategies and their outcomes. Apart from using donor grafts which are of adequate size for the recipient weight, portal hemodynamics are an important consideration to prevent early allograft dysfunction, graft failure and mortality. Summary: Understanding normal portal hemodynamics, how they change with the progression of cirrhosis, portal hypertension and changes after the implantation of a partial liver graft is key to managing patients with living-donor liver transplantation. If the intraoperative measurement of portal flow or pressure suggests graft portal hyperperfusion, inflow modulation strategies can be adopted. Splenic artery ligation, splenectomy and hemiportocaval shunts are well described in the literature. The proper selection of a donor to match the recipient’s anatomic, metabolic and hemodynamic environment and deciding which modulation strategy to use in which patient is an exercise in sound clinical judgement. Key message: The intraoperative assessment of portal hemodynamics in living-donor liver transplant should be standard practice. Inflow modulation in properly selected patients offers a point-of-care solution to alter portal inflow to the graft with a view to improve recipient outcomes. In patients with small (anatomically/metabolically) grafts, using inflow modulation can result in outcomes equivalent to those in patients in whom larger grafts are used.

Transplantology doi: 10.3390/transplantology4010005

Authors: Alexander Nikoloudis Irene Strassl Michaela Binder Olga Stiefel Dagmar Wipplinger Robert Milanov Christoph Aichinger Emine Kaynak Sigrid Machherndl-Spandl Veronika Buxhofer-Ausch Alexandra Böhm Andreas Petzer Ansgar Weltermann Dominik Wolf David Nachbaur Johannes Clausen

Background: Serotherapy with anti-T lymphocyte globulin (ATLG, Grafalon, formerly ATG-Fresenius) is established for the prevention of severe graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). The evidence from prospective studies is predominantly derived from a setting where methotrexate (MTX) and a calcineurin inhibitor (CNI) are used as the backbone of GVHD prophylaxis. The efficacy of ATLG in combination with CNI and mycophenolate mofetil (MMF) has not been investigated as much, particularly in terms of a direct comparison with its effects when combined with CNI/MTX. A total of 401 HSCTs from two Austrian transplant centers were retrospectively evaluated. We included peripheral blood transplants from early- or intermediate-stage (excluding advanced/refractory) hematological diseases from matched siblings or 10/10 or 9/10 matched unrelated donors with CNI/MTX or CNI/MMF prophylaxis, either without (n = 219) or with ATLG (n = 182). Overall, ATLG significantly reduced the risk for all-cause mortality by multivariate Cox analysis (HR 0.53; p = 0.002). Stratification by postgrafting prophylaxis type revealed a significant survival advantage for ATLG in the CNI/MMF cohort (HR 0.49; p = 0.001; n = 193), while its effect on survival in the CNI/MTX cohort was not significant (HR 0.87; p = 0.56; n = 208). In unrelated HSCT with CNI/MMF prophylaxis, ATLG exhibited its greatest survival benefit (HR 0.34; p = 0.001; n = 104). In the context of CNI/MMF, ATLG may provide even greater benefits than in the setting of CNI/MTX for post-grafting immunosuppression. Future prospective studies on ATLG should therefore focus on CNI/MMF-based transplants, which are widely performed in elderly or comorbid patients not expected to tolerate a standard course of MTX.

Transplantology doi: 10.3390/transplantology4010004

Authors: Maurizio Salvadori

Medicine has evolved from the so-called experience-based medicine to evidence-based medicine, which is now evolving into precision-based medicine [...]

Transplantology doi: 10.3390/transplantology4010003

Authors: Transplantology Editorial Office Transplantology Editorial Office

High-quality academic publishing is built on rigorous peer review [...]

Transplantology doi: 10.3390/transplantology4010002

Authors: Sushma Bhusal Hailey Hardgrave Aparna Sharma Lyle Burdine Raj Patel Gary Barone Neriman Gokden Emmanouil Giorgakis

Background: Kidney allografts with the presence of diffuse glomerular fibrin thrombi are typically rejected by most centers due to concern for poor allograft outcomes in the recipients. The aim of this study was to report our single center experience in the use of such deceased donor allografts. Methods: Retrospective single-center cohort study of kidney transplant recipients who received deceased donor allografts with moderate-to-severe diffuse glomerular fibrin microthrombi on the pre-implantation biopsy. Results: Three adult recipients received deceased donor kidney transplantation from donation after circulatory death donors. One patient was pre-emptive to dialysis at the time of transplant. The donors had moderate-to-severe diffuse glomerular fibrin thrombi on preimplantation biopsies with no evidence of cortical necrosis. Mean follow-up period was 196 days. None of the recipients developed delayed allograft function. The mean 3-month and 6-month creatinine were 1.6 and 1.5 mg/dL, respectively, with corresponding mean eGFRs (estimated glomerular filtration rates) of 45.7 and 47.3 mL/min/1.73m2. Conclusions: After excluding significant cortical necrosis by experienced transplant renal pathologist, otherwise transplantable kidney allografts with diffuse fibrin thrombi may be successfully transplanted in renal transplant recipients with good renal outcomes.