Search Results (150)

Despite their reduced viability, kidneys from donors-after-circulatory-death (DCD) increase the pool of transplantable kidneys. Molecular hydrogen (H₂) is emerging as a gas with therapeutic potential against graft injury. We investigated the effect of H₂ in an ex vivo porcine model of DCD kidney transplantation. Renal arteries of male Yorkshire pigs (n = 6) were clamped in situ for 60 min to induce ischemia, and ureters and arteries were cannulated to mimic DCD kidney injury. Upon nephrectomy, kidneys were flushed with UW solution or H₂-saturated UW solution and then preserved by machine perfusion at 4 °C for 4 h followed by a 4-h reperfusion period with warm autologous blood. Urine and arterial blood samples were collected hourly. H₂ preserved renal architecture, evidenced by significantly reduced tubular necrosis and renal expression of damage markers, which corresponded with the downregulated renal expression of pro-inflammatory genes compared to the UW-only group (p < 0.05). H₂ also markedly reduced levels of serum creatinine, BUN and intrarenal resistance, while flow rate, creatinine clearance and urine output were significantly higher, which positively correlated with Trx-1 and HO-1 expression in comparison with UW only group (p < 0.05). Improvement in renal graft quality and function is associated with Trx-1/HO-1 activation, suggesting preliminary clinical trials in kidney transplantation. Full article

Kidney transplantation is considered the best therapeutic option for patients affected by end-stage renal failure, but this possibility is limited by a shortage of donors. Living-donor kidney transplantation (LDKD) is a valuable option, frequently limited by immunological incompatibility between donor and recipient. This review will consider the possibility of performing living-donor kidney donation in the case of AB0 blood group incompatibility and the progress that has been made in this field. Kidney-paired donation is one possibility. This technique is the best option if there are numerous available pairs. This approach is possible because of national and international registries. The more diffuse technique is the desensitization of the recipients. Desensitization may be achieved in several ways, which are extensively discussed in this review. Recently, some published studies documented the possibility of enzymatically converting the A or B groups from the cells of the donor to the O group. This approach is only in a nascent stage but may represent the future, eventually associated with mild desensitization. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

Background/Objectives: Ischemia–reperfusion injury (IRI) contributes to graft dysfunction in solid organ transplantation, with the pancreas vulnerable due to its fragile vasculature. Endothelial glycocalyx (eGCX) disruption is central to this process. This study prospectively examined perioperative endothelial injury in pancreas transplantation. Methods: Fifty-two recipients were included, of whom 47 underwent simultaneous pancreas-kidney (SPK) transplantation and 5 pancreas retransplantation. Biomarkers of eGCX degradation (syndecan-1, heparan sulfate (HS) and hyaluronan) and endothelial injury (soluble thrombomodulin, VEGF and soluble VEGFR1) were measured in plasma preoperatively, 10 min after pancreas reperfusion, 24 h later, and at discharge. Associations with donor type and early post-transplant outcomes were explored. Results: A marker endothelial injury was evident within 10 min of pancreas reperfusion, before kidney implantation, characterized by increased syndecan-1, HS, and sVEGFR1, together with decreased VEGF. Hyaluronan peaked at 24 h, consistent with a broader systemic endothelial response. Controlled donation after circulatory death donors showed higher syndecan-1 levels at 10 min PR and higher VEGF at 24 h. Seven recipients developed pancreas graft loss, which was linked to lower VEGF at 10 min post-reperfusion and lower hyaluronan levels both before surgery and at discharge. Kidney acute tubular necrosis was related with higher preoperative HS and elevated 24 h sVEGFR1. Among recipients with functioning grafts, preoperative endothelial biomarkers were linked to postoperative complications. Conclusions: Pancreas transplantation triggers early endothelial injury and glycocalyx shedding, particularly in a predominant SPK setting. Perioperative endothelial biomarkers may have a value for early risk stratification after transplantation. Full article

Background/Objectives: Renal scintigraphy with 99mTc-MAG3 is a non-invasive tool for assessing early post-kidney-transplant function and detecting complications. While its utility in predicting delayed graft function (DGF) is established, evidence regarding its capacity to predict long-term graft survival remains limited. This study aimed to evaluate whether early post-transplant scintigraphy provides independent prognostic information for long-term graft survival. Methods: We conducted a retrospective cohort study of kidney transplantations performed at a single tertiary-care academic institution (2015–2019). Patients undergoing simultaneous multi-organ transplantation or experiencing complications precluding early scintigraphy were excluded. All included patients underwent 99mTc-MAG3 scintigraphy within 48 h post-transplantation. Renogram curves were categorized using the Heaf and Iversen classification (Grades 1–4). Univariate and multivariate Cox proportional hazards regression analyses were performed to assess death-censored graft survival. The study followed STROBE reporting guidelines. Results: Among the 317 included patients, renogram curves were distributed as follows: Grade 1 (n = 31, 9.8%), Grade 2 (n = 69, 21.8%), Grade 3 (n = 92, 29.0%), and Grade 4 (n = 125, 39.4%). The overall DGF incidence was 25.9%, with rates progressively increasing across the grades: 0% (Grade 1), 4.3% (Grade 2), 16.3% (Grade 3), and 51.2% (Grade 4) (p < 0.001). On multivariate analysis adjusting for recipient BMI, donation technique, Kidney Donor Risk Index (KDRI), and DGF, grafts with reduced uptake (Grade 4) demonstrated a significantly higher risk of graft loss compared to those with normal uptake (Grades 1–3 combined) (HR: 3.15; 95% CI: 1.34–7.40; p = 0.008). The mean follow-up was 45.6 months (IQR: 34.5–60). Conclusions: 99mTc-MAG3 scintigraphy performed within 48 h of kidney transplantation provides independent prognostic information for long-term graft survival. The Grade 4 renogram pattern identifies a high-risk subgroup with over threefold increased risk of subsequent graft loss. These findings support the integration of early scintigraphy into post-transplant risk stratification protocols, though prospective validation is warranted. Full article

Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities. Full article

Background: Uterus transplantation (UTx) is an emerging treatment for absolute uterine factor infertility. However, the use of deceased donors is limited, and donation after circulatory death (DCD) has not yet been utilized. Ischemic injury remains a major barrier, particularly compared with living donor procedures. Hypothermic oxygenated perfusion (HOPE), which has shown protective effects in heart, liver, and kidney transplantation, may offer similar benefits for uterine grafts. Methods: We report the first series applying HOPE to human uteri to improve preservation and enable metabolic injury assessment during perfusion. Six uteri (3 DBD, 3 DCD; median donor age 53 years) underwent 8 h of HOPE following procurement, while paired tissue controls were preserved using static cold storage (SCS). Perfusion was delivered using a pressure-controlled system (15 mmHg, 10 ± 1 °C, VitaSmart^®). Perfusate and tissue samples were analyzed for mitochondrial injury, inflammation, and transcriptional responses. Results: HOPE maintained stable flows (70–150 mL/min), delivered high oxygen levels (pO₂ ≈ 1000 hPa), and increased tissue ATP levels. Stratification based on perfusate flavin mononucleotide (FMN) release identified grafts with greater Complex I/II injury. HOPE was associated with lower levels of mitochondrial injury markers and inflammatory signals, preserved tissue architecture, and promoted gene expression patterns consistent with metabolic recovery compared with paired SCS tissue controls. Conclusions: These findings suggest that HOPE may serve as a preservation approach that enables metabolic and ischemic injury assessment and may facilitate broader use of deceased donor uteri for transplantation. Full article

End-stage kidney disease (ESKD) is a global health challenge, with kidney transplant demand outstripping supply. Allotransplantation remains the gold standard for treatment but organ scarcity leads to prolonged waiting times and high mortality. Xenotransplantation, using genetically modified porcine kidneys, offers a novel and potentially sustainable solution. Genetic engineering and immunosuppression advances have enabled xenotransplantation to transition from a theoretical possibility to feasible solution. This review explores the evolution of xenotransplantation, the scientific advancements in overcoming immunological barriers, and emerging clinical data. Furthermore, we discuss emerging approaches such as central immune tolerance induction, the ongoing risks of cross-species infection, and the ethical and environmental considerations inherent to scaling up porcine organ donation. With the commencement of the first formal clinical trials, progress in the field could transform kidney transplantation, though questions remain regarding long-term outcomes and societal impact. Full article

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. Full article

Background/Objectives: Kidney donation remains a critical component of addressing end-stage renal disease. This study examines differences in awareness, willingness to donate, and concerns related to kidney donation among medical and non-medical university students. By comparing these groups within the context of Croatia’s presumed-consent system for organ donation, the study provides insights into how educational backgrounds shape attitudes in a setting with high transplantation rates but limited data on young adults. Methods: A cross-sectional observational study targeted at medical and non-medical university students in Croatia. Data were collected from 640 participants via a self-administered, close-ended, structured questionnaire with 33 items divided across three sections. Responses were analyzed using IBM SPSS Statistics program (v. 30.0), to identify significant differences. Due to the cross-sectional design, causal relationships could not be inferred. Results: Overall, 190 students (28.7%) reported willingness to donate a kidney during their lifetime, which was more common among medical students (N = 59; 39.0%) than non-medical students (N = 131; 26.8%). Collectively, willingness to donate postmortem was high in both groups (N = 527; 82.3%), as was willingness in a brain-dead state (N = 448; 70.0%). Medical and non-medical students mostly cited perceived health risks as a concern and concerns related to surgical complications. Regarding information sources, 33.2% of students reported inadequate knowledge of kidney donation, with social media and internet searches cited more frequently than healthcare professionals. Conclusions: Our findings indicate that medical and non-medical students exhibit distinct gaps in knowledge, risk perception and willingness toward kidney donation. Within Croatia’s presumed-consent framework, these findings highlight the importance of targeted educational strategies to support informed decision-making among future generations. Full article

Background/Objectives: Kidney transplantation remains the most effective treatment for patients with end-stage kidney disease, increasing both survival and quality of life. There are concerns regarding the long-term outcomes of donors in developing countries, as kidney transplants are predominantly performed from living donors. This study was conducted to evaluate the long-term clinical outcomes of living kidney donors, with a particular focus on kidney and cardiovascular health. Methods: We retrospectively reviewed the records of 232 individuals who underwent donor nephrectomy between January 2011 and November 2022. Cardiovascular events, mortality, chronic kidney disease, hypertension, and newly onset diabetes were assessed. Estimated glomerular filtration rate (eGFR) values were employed to monitor kidney function over time. Results: Living kidney donors were monitored for a median of 6 years (IQR: 4–9 years). During the follow-up period, 18.9% of donors experienced a decline in eGFR to below 60 mL/min/1.73 m²; however, none progressed to end-stage kidney disease. Of the cohort, 20 (8.6%) had newly onset proteinuria and none had proteinuria before transplantation. Although there were no recorded deaths from cardiovascular causes, 4.3% of donors experienced major adverse cardiac events. 12.3% of donors had newly diagnosed hypertension following transplantation, and 20.2% of donors had hypertension overall. Lower baseline eGFR, treated as a continuous variable in the logistic regression model, was independently associated with a higher likelihood of post-donation eGFR < 60 mL/min/1.73 m² (OR: 0.91; 95% CI: 0.88–0.94; p < 0.001). Post donation proteinuria (OR: 6.61; 95% CI: 1.98–22.07, p: 0.002) was also identified as independent risk factors for decline in eGFR to below 60 mL/min/1.73 m². Diabetes mellitus was found to be a significant predictor of newly onset hypertension. Conclusions: A considerable percentage of the donors experienced gradual deterioration in kidney function, even though none of them developed kidney failure necessitating dialysis. The prevalence of obesity and chronic kidney disease was higher post-donation compared to the general population, indicating the need for structured long-term monitoring. Full article

At the beginning of the COVID-19 pandemic, SARS-CoV-2-positive donors were not considered eligible for organ donation. The Italian National Transplant Centre has gradually introduced measures to prevent donor-to-recipient transmission of SARS-CoV-2 infection through organ transplantation. The current national screening protocol for deceased SARS-CoV-2-positive donors recommends molecular testing of donor lower respiratory tract (LRT) samples, graft biopsies and organ perfusion fluids. The aim of the study is to describe the 3-year experience of protocol application in a northern region of Italy. From 1 January 2022 to 31 January 2025, a total of 132 samples were analyzed (29 liver biopsies, 35 kidney biopsies, 68 perfusion fluids) from 40 organ donors with an active or resolved SARS-CoV-2 infection. SARS-CoV-2 PCR on LRT samples was positive in 26/40 (65%) donors, negative in 11/40 (27.5%) cases and in the remaining 3 (7.5%) the PCR result was unknown. Overall, 65 organs were transplanted into 60 recipients. All processed graft biopsies and organ perfusion fluid samples tested negative for SARS-CoV-2 RNA. Our data suggest that the utilization of non-lung donors with resolved or active SARS-CoV-2 infections who died of other causes appears justified and safe. Full article

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. Full article

Background and Objectives: The use of controlled donation after circulatory death (cDCD) donors has significantly increased during the past decades and successfully expanded the donors’ pool. However, warm ischemia may have detrimental effects on graft function. Italian Law requires a no-touch period of at least 20 min, which is much longer compared to the 5 min accepted in most European countries. Materials and Methods This is an Italian single-centre retrospective review of all cDCD procedures performed from April 2021 to June 2025. Patients with severe brain injury undergoing withdrawal of life-sustaining therapy (WLST) were considered for cDCD. After cardiac arrest and a no-touch period of 20 min, organ reperfusion was performed using abdominal or thoraco-abdominal normothermic regional perfusion (NRP) through femoral vessels cannulation. The primary endpoint was 30-day graft survival; secondary endpoints included: incidence of primary non-function (PNF) and non-anastomotic biliary stricture (NAS) in liver transplantation, PNF and delayed graft function (DGF) in kidney transplantation, primary graft dysfunction (PGD) in heart and lung transplantation, and recipient’s survival. Results: A total of 52 patients, 33 (63%) males, median age 74 (65–79) years, underwent WLST during the study period and were included in the cDCD program. Median functional warm ischemic time (WIT), total WIT, asystolic phase, and NRP duration were 37 (34–40), 40 (37–42), 24 (23–26), and 192 (166–212) min, respectively. A total of 123 organs (46 livers, 61 kidneys, 8 hearts, and 8 lungs) were considered suitable for transplantation, procured, and successfully transplanted in 115 recipients. We report the early and mid-term outcomes of 84 recipients, including 41 liver recipients, 32 kidney recipients, and 8 heart recipients transplanted at the Azienda Ospedaliera Universitaria Integrata of Verona, and 3 lung recipients transplanted at the Azienda Ospedale Università of Padova. The 30-day graft survival was 95% in liver recipients, 97% in kidney recipients, and 100% in heart and lung recipients. PNF was observed in two liver recipients, and PGD in two lung recipients. DGF was recorded in 3 (9%) kidney recipients. Six recipients died during the follow-up, and the mean survival time was 3.9 ± 0.1 years. Conclusions: Solid organ transplantation using cDCD donors is feasible and provides excellent early and mid-term results despite longer donor asystolic times. Larger data and longer follow-up are necessary to confirm these promising results. Full article

Background: Uncontrolled donation after circulatory death (uDCD) remains underutilized globally, despite critical organ shortages. We report outcomes from Israel’s uDCD kidney transplant program compared with the matched donation after brain death (DBD) recipients. Methods: This retrospective cohort study analyzed all uDCD kidney transplants performed at the Rabin Medical Center between January 2018 and December 2024, compared with DBD transplants during the same period. Propensity score matching (1:3 ratio) was performed using recipient demographics, comorbidities, and donor characteristics. Primary outcomes included delayed graft function (DGF), graft failure, and patient survival. Results: Among 92 kidney transplants, 21 (22.8%) were from uDCD donors. After propensity-matching (21 uDCD, 63 DBD), significant baseline differences persisted: uDCD recipients were younger (47.2 ± 11.8 vs. 57.5 ± 10.9 years, p < 0.001) despite a similar dialysis vintage (7.2 ± 3.2 vs. 7.7 ± 3.7 years, p = 0.569). Warm ischemia time was 58.5 ± 12.3 vs. 3.0 ± 0.0 min (p < 0.001), and cold ischemia time was longer in uDCD (13.7 ± 5.9 vs. 8.4 ± 2.5 h, p < 0.001). DGF occurred in 90.5% of uDCD versus 54.1% of DBD recipients (p = 0.006). Graft failure was markedly higher in uDCD (28.6% vs. 1.6%, p = 0.001), yet mortality was lower (14.3% vs. 27.9%, p = 0.339). After a median follow-up of 60 months (IQR 48–72) for both groups, the death-censored 5 year graft survival rate was 71.4% for uDCD versus 98.4% for DBD (p < 0.001). Conclusions: Despite higher rates of DGF and graft failure, uDCD kidney transplantation demonstrated an acceptable 5 year patient survival rate in carefully selected younger recipients. These findings support cautious expansion of uDCD programs with rigorous recipient selection criteria and realistic outcome expectations. Full article