Background: Sepsis is one of the leading causes of early death after a liver transplant, with a frequency of up to 45% and a high death rate of 50% in more severe forms. Standard diagnostic and therapeutic algorithms are often not applicable to this specific population, where immunosuppression, reperfusion injury, and systemic inflammation overlap and generate a clinical picture that is significantly different from sepsis in immunocompetent patients. Methods: This paper analyzes the available literature and clinical experiences of characteristic immune and hemodynamic profiles of sepsis after liver transplants. Biomarkers (IL-6, IL-10, HLA-DR, lactate, and IgM) are discussed as tools for assessing immune status and guiding timely interventions, including the early application of continuous renal replacement therapy (CRRT) and the selective use of IgM-enriched immunoglobulins. Results: Sepsis after liver transplantation frequently unfolds in two phases, an initial hyper-inflammatory response driven by cytokine release and reperfusion injury and a second phase of secondary immunoparalysis characterized by reduced HLA-DR expression and increased anti-inflammatory signaling. The immunometabolic shift appears to influence the clinical course and may inform therapeutic decision-making. The immunoparalysis phase is accompanied by mitochondrial dysfunction and impaired vascular reactivity. This type of mechanism contributes to hemodynamic instability and a reduced response to standard therapy. Individualized monitoring and early use of hemofiltration and immunomodulatory measures can improve results in carefully selected patients. Conclusions: In this setting, an individualized immunometabolic approach may complement standard sepsis management in liver transplant recipients. The introduction of biomarkers of immune function into routine practice and the recognition of early signs of exhaustion of the immune response can assist in timely therapeutic decision-making and improve survival.

Background/Objectives: Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifactorial and incompletely understood. This narrative review summarizes contemporary evidence (2015-2025) on therapeutic strategies for uremic pruritus, with an emphasis on emerging treatments and evolving mechanistic insights. Methods: A PubMed search was conducted for original clinical studies published between 1 January 2015, and 31 October 2025, evaluating treatments for uremic pruritus in adult hemodialysis patients. Eligible study designs included randomized controlled trials and observational interventional studies. Non-English articles, pediatric studies, peritoneal dialysis studies, reviews, case reports, and studies of mixed-etiology pruritus were excluded. Earlier literature was reviewed to contextualize epidemiology and pathophysiology. Results: The review identifies multiple interacting mechanisms-including uremic toxins, immune dysregulation, mineral abnormalities, xerosis, neuropathic changes, and dysregulated opioid signaling-contributing to itch generation. Topical therapies, especially emollients and humectants, consistently improved symptoms with excellent safety profiles. Optimization of dialysis adequacy and membrane selection showed benefit in selected patients. Among systemic therapies, gabapentinoids demonstrated the most robust efficacy but required cautious dosing. Sertraline, nalbuphine, and difelikefalin showed significant antipruritic effects in controlled trials. Emerging therapies, including AST-120, omega-3 fatty acids, and the biologic dupilumab, demonstrated promising but preliminary results. Conclusions: Management of uremic pruritus requires a multifaceted, individualized approach integrating skin-directed therapies, dialysis optimization, and targeted systemic treatments. Ongoing research is needed to identify reliable biomarkers and to develop safer, more effective, mechanism-based therapies.

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.

BACKGROUND:Kidney transplant recipients are at increased risk of severe varicella-zoster virus (VZV) infection due to chronic immunosuppression. While antiviral therapy is the mainstay of treatment, the role of adjunctive VZV-specific intravenous immunoglobulin (VZV-IVIG) in complicated disease remains insufficiently defined. METHODS:We present a case series of 3 kidney transplant recipients with complicated VZV infection treated with VZV-IVIG in addition to standard antiviral therapy at a tertiary transplant center between 2024 and 2025. Clinical presentation, virological course, immunosuppression management, graft function, and outcomes were analyzed. RESULTS:All patients were receiving maintenance immunosuppression and developed severe VZV manifestations, including disseminated primary infection with visceral and ocular involvement and herpes zoster with suspected ocular/visceral involvement. VZV-IVIG was administered as a single dose, short weekly course, or prolonged monthly therapy based on disease severity and virological response. Treatment was well tolerated, with no significant adverse events or deterioration in renal allograft function. Clinical stabilization and regression of cutaneous and systemic manifestations were observed in all cases. One patient with panuveitis and persistent viremia required repeated VZV-IVIG courses and achieved gradual virological suppression with prevention of further end-organ damage, although residual visual impairment remained. CONCLUSIONS:Adjunctive VZV-IVIG may be a useful and safe therapeutic option in selected kidney transplant recipients with severe, refractory, or organ-threatening VZV infection, particularly in cases of persistent viremia or ocular involvement. Larger studies are needed to define optimal patient selection, dosing strategies, and treatment duration.

Objective To perform comprehensive validations of the integrative Box (iBox) system, a prediction model for long term risk of kidney allograft failure, for extension of its context of use in clinical trials as well as for its wider implementation in clinical practice.Design Extended validation study.Setting Paris Transplant Group database (comprising kidney recipients with transplantations between 1 January 2005 and 1 January 2014) and European, North American, and South American hospitals (comprising recipients of kidneys transplanted beween 1 January 2000 and 1 January 2022). Patients were followed until 1 November 2024.Participants 12 683 kidney tranplant recipients from 21 academic centres in Europe, North America, and South America; 4000 patients in the derivation cohort and 8683 in the validation cohorts.Main outcome measures Performance of the iBox, including flexible iBox versions in specific clinical contexts (race-free estimated glomerular filtration rate (eGFR) equations (ie, without including race as a factor in the calculation), in specific clinical contexts (initial nephropathy recurrence, BK virus associated nephropathy, and different immunosuppressive strategies), and over-extended follow-up periods. Predictive performance was assessed by discrimination, calibration, overall fit, and clinical utility.Results 12 683 kidney transplant recipients were included in the study (n=4000 in the derivation cohort and n=8683 in the validation cohorts). Median follow-up time after risk evaluation was 5.78 years (interquartile range (IQR) 3.51-7.00) in the derivation cohort and 4.68 years (2.48-7.00) in the validation cohorts. 549 (13.7%) and 991 (11.4%) patients had graft loss in the derivation and validation cohorts, respectively. All versions of the iBox algorithm maintained good discrimination and overall fit performance in the derivation and validation cohorts (C index range 0.79-0.87, Brier scores 0.08-0.11). Calibration was adequate in some but not all external validation cohorts, with trends toward overestimation or underestimation of predicted risks. Decision curve analysis showed positive and comparable net benefit for all iBox algorithms across decision thresholds up to 40% in the derivation cohort (net benefit 0.07-0.08 at 20% threshold) and validation cohorts (net benefit 0.03-0.11 at 20% threshold). Accounting for the competing risk of death with a functioning graft resulted in similar performance, except for calibration which varied across cohorts, without any model consistently outperforming any other model. The model performed well with different race-free eGFR equations (C index 0.81), in various clinical scenarios, including disease recurrence and BK virus nephropathy, with different immunosuppressive strategies, such as calcineurin inhibitors and mTOR (mechanistic target of rapamycin) inhibitors (C index range 0.74-0.87), and when extending the prediction period to 10 years after risk evaluation (C index 0.79). The iBox predictive performance was not modified when various histological indices were used. The iBox was also superior to eGFR slope (C index 0.81 v 0.62) and circulating anti-HLA donor specific antibodies (C index 0.81 v 0.57) in its predictive ability.Conclusions In this study, the robust predictive performance of the iBox system across diverse real world settings and clinical scenarios was shown. These results highlight the versatility and reliability of the iBox system, and support its use for risk stratification in routine clinical practice and as a surrogate endpoint for clinical trials.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder of the alternative complement pathway characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. It has a genetic background or may be triggered by viral infections and certain medications, such as immunosuppressants. We present a case of post-kidney transplant development of aHUS in a genetically predisposed individual with an acute adenoviral infection. A 25-year-old male with known chronic kidney failure and subsequent renal transplantation was admitted to hospital due to respiratory symptoms, fever, leukopenia, thrombocytopenia, hemolytic anemia and deteriorating renal graft function. Imaging revealed a consolidation in lower right lung lobe with pleural effusion, while bronchoscopy confirmed adenovirus infection. The findings suggested that the patient suffered from thrombotic microangiopathy, causing an acute kidney failure, aggravated by an adenoviral infection. Empirical treatment with the C5 complement component inhibitor ravulizumab was initiated, and genetic testing for complement abnormalities was performed. Following ravulizumab administration, the patient became afebrile, inflammatory markers decreased and both cytopenia and graft function improved. A CT scan marked regression of lung consolidation and effusion. Complement analysis later confirmed inherited defects predisposing to aHUS. The patient was discharged home in good condition with stable kidney allograft function. This case supports the increasing evidence linking adenoviral infections with aHUS onset and highlights the importance of considering this rare diagnosis in predisposed patients with compatible clinical and laboratory findings. Early recognition enables timely intervention, which is essential for preventing irreversible kidney damage that could be fatal.

Background: Balkan nephropathy (BEN), caused by chronic dietary exposure to aristolochic acid (AA), is a tubulointerstitial kidney disease strongly associated with upper-tract urothelial carcinoma (UTUC). Patient and graft survival, the cumulative incidence and timing of post-transplant UTUC, and the burden of non-urothelial malignancy after kidney transplantation remain poorly defined. Methods: We retrospectively analyzed all patients with BEN as the primary cause of end-stage kidney disease transplanted at University Hospital Center Zagreb between October 1973 and December 2023. Outcomes included patient and graft survival, the incidence and timing of post-transplant UTUC, and burden of non-urothelial malignancies. Results: Of 2282 kidney transplants performed in the study period, 44 (2%) were in patients with BEN. The median age at transplantation was 56 years, and the median dialysis vintage was 3.7 years. After 10 years (median) of follow up, among 34 patients with adequate follow-up, 16 (47%) developed a de novo malignancy: eight (24%) UTUC, one renal cell carcinoma, four other solid tumors, and three hematological. UTUC was diagnosed between 6 months and 15 years post-transplant (median 7 years); five of eight patients died within one year of diagnosis. Five- and ten-year patient survival rates were 82% and 54.5%. Conclusions: Kidney transplantation in patients with BEN carries a lifelong cancer risk dominated by UTUC. Prophylactic bilateral nephroureterectomy should be the default management strategy when feasible, with lifelong surveillance extending beyond the urothelium.

Sphingolipids are a complex group of lipids that are becoming increasingly important in many aspects of disease and cell physiology. They are composed of a long-chain sphingoid base backbone, a long-chain fatty acid linked by an amide bond, and one or more polar head groups the structures of which are characterized by different sphingolipid subtypes such as ceramide, sphingomyelin, and glycosphingolipids. The metabolism of these lipids plays an integral role in scaling body functions. They take involvement in the membrane domains and signaling, inflammation, cell proliferation, death, migration, and central nervous system development. Due to their discovery as potent messenger and signaling molecules, sphingolipids have lately attracted interest and are now thought to be potential therapeutic targets for a number of diseases. Here, we provide a thorough overview of sphingolipid metabolism and numerous biological functions inside the cell. Additionally, we draw attention to the sphingolipid involvement in a number of diseases, such as cancer, cystic fibrosis, and inflammatory disease, Alzheimer’s disease, Parkinson’s disease, and diseases related to lysosomal storage.

Background: Balkan nephropathy (BEN) is an environmental form of aristolochic acid nephropathy (AAN) strongly associated with upper urinary tract urothelial carcinoma (UTUC). Clinical diagnosis remains challenging, and misclassification is frequent. The study reassessed BEN diagnoses in kidney transplant recipients from rural farming areas who did not undergo prophylactic bilateral nephroureterectomy and evaluated post-transplant outcomes. Methods: In this retrospective single-centre study, we analysed 12 kidney transplant recipients from rural Balkan farming regions. BEN diagnoses were reevaluated according to international consensus criteria. Key endpoints included patient and graft survival, post-transplant clinical course, and UTUC characteristics. Results: Upon reassessment, three of the six patients initially diagnosed with BEN were reclassified as having BEN. Among the remaining six patients, four were reclassified as having sporadic BEN. Overall, only 33% of patients had a diagnosis concordant with their admission records. During a median follow-up of 6.8 years (IQR 2.1-15.8), UTUC developed in seven out of 12 patients. The UTUC cases were predominantly high-grade and multifocal, and they were identified as the leading cause of death. Five-year patient and graft survival rates were 71% and 100%, respectively. Conclusions: BEN is frequently misdiagnosed or misclassified in kidney transplant candidates from rural farming areas. Despite excellent graft survival, the high incidence of post-transplant urothelial carcinoma underscores the necessity of accurate diagnosis and the consideration of prophylactic bilateral nephroureterectomy. Lifelong intensive surveillance is essential not only for patients from established BEN regions but also for individuals from other rural farming areas at risk for sporadic BEN.

Testicular cancer (TC) is the most common type of cancer among young men aged 25 to 45. This study represents the first population study of TC in kidney transplant recipients (KTRs). We conducted a multicentric, multinational, cross-sectional study across nine transplant centers in Croatia, Serbia, Montenegro, Slovenia, and Bosnia and Herzegovina. All KTRs over 18 years old who were regularly monitored at their transplant centers were included. Data were collected from electronic medical records at these centers. Out of the 4426 KTRs who participated in our study, six (0.14

Cytomegalovirus (CMV) infection poses significant challenges in solid organ transplant (SOT) recipients, impacting graft outcomes, morbidity, and in some cases survival. The ESOT CMV Workshop 2023 convened European experts to discuss current practices and advances in the management of CMV with the aim of improving the quality of life of transplant recipients. Discussions covered crucial areas such as preventive strategies, diagnostic challenges, therapeutic approaches, and the role of cell-mediated immunity (CMI) monitoring. Despite advances, ambiguity persists in optimal CMV management across European transplant centers. Preventive strategies, including universal prophylaxis and pre-emptive therapy, are effective but consensus is lacking with respect to the preferred approach. Diagnostic challenges such as standardization of viral load thresholds and detection of end-organ disease complicate timely intervention. While newer therapies like maribavir hold promise for treating complicated CMV infections, sustaining viral clearance remains a challenge. Integrating CMI monitoring into CMV management could personalize treatment decisions but has limitations in in terms of predictive value and accessibility. Further research is needed to fill these gaps and optimize CMV management. The collaborative efforts, led by the European Society for Organ Transplantation (ESOT), aim to standardize and improve CMV care, ensuring better outcomes for SOT recipients.

Background: Bone morphogenetic proteins (BMPs) are growth factor proteins with various developmental and functional roles. They are associated with chronic kidney disease and vascular alterations such as atherosclerosis and calcification. In kidney transplantation, BMP 2 has been associated with delayed graft function, while downregulation of BMP 2, 4, and 6 in kidney grafts has been associated with interstitial fibrosis and atrophy. Rhis study was designed to investigate the associations of recipient artery BMP expression with long-term kidney allograft loss and mortality. Methods: A prospective cohort study included 58 kidney transplant recipients from January 2012 to March 2013, monitored for up to 10 years. Bone morphogenetic protein expression in recipient epigastric arteries was evaluated using immunohistochemistry. Selected outcomes included death-censored graft loss (DCGL), death, and a composite endpoint (graft loss or death). Data were analyzed usingt-tests, chi-squared tests, logistic regression, and Kaplan-Meiersurvival analysis. Results: At 5 years, 88% of patients survived, with 81% maintaining graft function. BMP4m and BMP6m positivity were associated with 100% survival and graft function at both 5 and 10 years. At 10 years, 74% of patients survived, with 67% maintaining graft function. BMP4e staining was associated with better composite outcomes at 10 years. No significant associations were found between BMP expression and DCGL or death. Notably, older age at transplantation and lower creatinine clearance at 1 year post-transplant were linked to higher rates of adverse outcomes. Conclusions: This study suggests that BMP expression does not correlate with long-term outcomes after kidney transplantations. Although BMP4 expression in the endothelium was associated with survival and graft function at 10 years post-transplant in this cohort, this correlation was lost when adjusting for other factors. Further research with larger cohorts is needed to validate these findings and explore the potential prognostic roles of BMPs in kidney transplantation.