Optimizing the Diagnosis of Ureteral Complications After Kidney Transplantation Using Retrograde Multidetector Computed Tomography Urography: A Case Series

Israel and the United States are both high-income nations committed to providing universal access to kidney replacement therapy (KRT) for patients with end-stage kidney disease (ESKD). Despite this shared principle, the clinical and economic burden of ESKD is substantial, and each country has developed distinct strategies to deliver and finance care. This manuscript presents a comparative analysis of epidemiology, treatment modalities, and health system approaches to ESKD management in Israel and the United States, reviewing trends in dialysis prevalence, modality utilization, and kidney transplantation between 2012 and 2022, alongside differences in health policy, reimbursement structures, and cost-containment strategies. The United States, which maintains the largest ESKD population worldwide, is characterized by high dialysis prevalence and extensive federal funding through Medicare. Israel, while smaller in scale, demonstrates unique patterns of care shaped by universal health coverage and cost-regulation mechanisms. Marked differences are evident in dialysis prevalence, transplantation rates, and per-patient expenditures. Comparative evaluation of these two health systems illustrates how countries with similar commitments to universal access have developed divergent models for financing and delivering KRT, offering important insights into the impact of health system design on patient care, cost management, cultural differences, and the opportunity to learn from each other.

Relying on a single primary endpoint in randomized controlled trials (RCTs) is often infeasible, for example due to rare or heterogeneous events. Regulatory guidance therefore allows multiple endpoints, but different analytical strategies address different scientific questions and null hypotheses, even when applied to the same set of variables. We explored three approaches to consider multiple endpoints in the primary analysis of RCTs, as stated in the FDA and EMA guidelines on multiplicity: (i) a composite endpoint (CE), (ii) multiple testing and multiplicity correction (MTMC), and (iii) a hierarchical non-parametric procedure, called generalized pairwise comparisons (GPC). Using clinical trial simulations, we compared these strategies' power in two-arm RCTs perform when testing strategy-specific hypotheses across a range of scenarios reflecting endpoint prioritization, correlation between endpoints, and opposing treatment effects. When testing time-to-event endpoints, global testing strategies (CE and GPC) generally achieved higher power than MTMC. However, we also demonstrate that global procedures may yield statistically significant results even when treatment effects are heterogeneous across endpoints, underscoring the importance of careful interpretation and component-wise assessment. As trials increasingly use multiple endpoints, understanding the trade-off between statistical efficiency and interpretability, and provide practical guidance for choosing endpoint definitions and primary analysis strategies in future trials.

Background/Objectives: To evaluate the outcome of developing BKPyV-DNAemia and presumptive BKPyV-nephropathy (BKPyV-DNAemia ≥ 104 copies/mL for more than 2 weeks) within the first 2 years post-transplant in a Belgian population of renal transplanted children. Methods: All children transplanted between 1 January 2010 and 31 December 2022 at Queen Fabiola Children’s University Hospital, Brussels (HUDERF) and at University Hospitals Leuven (UHL) were included in this retrospective study and 86 were followed for at least 2 years post-transplantation. Results: Within the first 2 years, 11/86 (13%) patients developed BKPyV-DNAemia ≥ 104 copies/mL (82% within the first 6 months). Among the 11 patients, 7 underwent a biopsy, of whom 4 were confirmed to have biopsy-proven BKPyV-nephropathy. Of those 11 patients, 4 (36%) developed an acute cellular rejection following immunosuppression reduction. The median eGFR at 2 years post-transplantation was 69 mL/min/1.73 m2 (IQR: 59–79) in the seven patients with presumptive BKPyV-nephropathy and 40 mL/min/1.73 m2 (IQR: 39–41) in the four with biopsy-proven BKPyV-nephropathy. At last follow-up visit, the median eGFR was 65 mL/min/1.73 m2 (IQR: 59–71) in the children with presumptive BKPyV-nephropathy, and 28 mL/min/1.73 m2 (IQR: 20–34) in the patients with biopsy-proven BKPyV-nephropathy. No risk factors for developing BKPyV-DNAemia were identified. Conclusions: Our study confirms that while BKPyV-DNAemia monitoring is essential in pediatric kidney transplant recipients, decisions based solely on viral load risk overtreatment and immunological complications. A personalized approach integrating viral, clinical, and immunological markers is urgently needed to balance infection control with graft preservation.

Human leukocyte antigen (HLA)-DR mismatches are known to increase the risk of graft rejection following kidney transplantation (KT). Especially in KT using grafts of lower quality from expanded criteria donors (ECD), the immune response plays a critical role. Therefore, the aim of this study was to investigate the impact of HLA-DR mismatches on both short- and long-term outcomes in primary ECD KT. 537 KT recipients were stratified into four groups based on their HLA-DR mismatch status [absent (−) or present (+)] and donor type [standard criteria donor (SCD) or ECD]: (1) SCD-DR-( N = 126), (2) SCD-DR+ ( N = 167), (3) ECD-DR- ( N = 60) and (4) ECD-DR+ ( N = 184). Clinicopathological characteristics, transplant outcomes and survival were evaluated across the groups. Rejection-free graft survival was significantly decreased in recipients of ECD-DR + KT ( P = 0.005). In comparison with ECD-DR- KTs, ECD-DR + KTs were associated with a significantly reduced graft survival (15.1 vs. 10.7 years; P = 0.034). After adjusting for relevant cofactors using multivariate Cox regression analysis, HLA-DR mismatch remained an independent predictor of graft rejection and graft survival in ECD kidney grafts. These results suggest that HLA-DR compatibility should be considered in allocation protocols for this donor category to improve long-term outcomes.

Patients with chronic kidney disease who undergo kidney transplantation are at risk of acute illness, acute graft failure, and intensive care admission in the years following transplantation. To identify individual risk factors, assess the effect of immunosuppression, and evaluate outcomes including loss of graft function in aEuropean setting, we analyzed 266 intensive care unit (ICU) admissions of kidney transplant recipients (KTRs) with severe illness between 2005 and 2019. Admission to the ICU occurred predominantly 12months or later after transplantation, with amedian time of 52.7months. Overall mortality was 12.8% and was associated with infections in 70.6% of cases. Acute immunosuppressive therapy for rejection, rather than primary induction or immunosuppressive regimens, correlated with critical illness in 53% of cases. The median time to ICU admission was 1.2years. Of the survivors, 12.1% lost graft function and remained on dialysis at discharge. In univariate and multivariate analyses, we found that SAPS (Simplified Acute Physiology Score)II values and vasopressor use were significantly associated with mortality. Overall, KTRs are at risk of critical illness, especially beyond 1year post-transplant. Rejection therapy and older age increase the risk of critical illness.

Objective To analyze the risk factors of hyperkalemia during kidney transplantation, and to construct the prediction model of nomogram. Methods 162 cases of renal transplant patients in our hospital from January 2020 to September 2024 were included. The clinical data of the patients were retrospectively analyzed. According to whether hyperkalemia occurred during the operation, the patients were divided into non hyperkalemia group and hyperkalemia group. The related factors of hyperkalemia in renal transplant patients were analyzed by multivariate logistic regression, and the nomogram model was constructed. Results Among 162 renal transplant patients, 59 cases (36.42%) had high potassium during operation. Univariate analysis showed that the pre-operative blood potassium, pulse pressure, and hemodialysis time of the high potassium group were higher than those of the non high potassium group, and the pH value of the high potassium group was lower than that of the non high potassium group, the difference was statistically significant ( P < 0.05). The results of logistic regression analysis showed that high preoperative blood potassium, low preoperative pH value, large pulse pressure, and long hemodialysis time were risk factors for Hyperkalemia during kidney transplantation surgery ( P < 0.05). The area under the ROC curve for the training set and validation set of the nomogram model constructed based on the aforementioned risk factors was 0.933 (95% CI: 0.885-0.981, P < 0.05), 0.798 (95% CI: 0.662–0.935, P < 0.05). The sensitivity, specificity, logit value, and cutoff value were 0.892, 0.872, −0.625, 0.6 and 0.862, 0.700, −0.159, 0.5, respectively. The calibration curve and decision curve results indicate that the model has high predictive performance and clinical application value. Conclusions High preoperative serum potassium, low preoperative pH, high pulse pressure, and long hemodialysis time are the risk factors of hyperkalemia in renal transplantation. According to the risk factors, constructing nomogram model to predict hyperkalemia in renal transplantation has high clinical value.

ABSTRACT The presence of donor‐specific antibodies (DSAs) is strongly associated with antibody‐mediated rejection (AMR) and worse allograft outcomes. The current gold standard method for detecting anti‐human leukocyte antigens (HLA) antibodies is based on the binding to HLA molecules, which are immobilized on beads. However, this assay may lead to the modification of the tertiary structure of the molecules and exposure of cryptic epitopes, thus resulting in aberrant false‐positive and false‐negative reactivity. With the increasing reliance on virtual crossmatching (comparing anti‐HLA antibodies identified using the single antigen bead (SAB) assay to the donor HLA typing to identify DSAs) instead of a physical crossmatch, native and full‐length HLA proteins are critical for accurate HLA antibody identification. In this study, we incorporate native and full‐length HLA into phospholipid bilayer nanodiscs to form stable HLA‐nanodisc (HLA‐ND) complexes in a native‐like membrane environment that maintains structure and prevents denaturation for anti‐HLA antibody identification. Using these HLA‐ND complexes immobilized on beads, we show successful DSA identification with serum from kidney transplant recipients. Furthermore, we introduce a novel bioluminescence‐based bead‐free homogeneous immunoassay for detecting anti‐HLA antibodies using HLA‐ND complexes. This platform has the potential to accurately detect multiple anti‐HLA antibodies before and after solid organ transplantation.

L’infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Des nouveautés dans les stratégies de sa prise en charge chez le patient transplanté rénal existent désormais. En effet, dans les dernières recommandations internationales, le létermovir peut être proposé lors d’une stratégie prophylactique chez des patients à haut risque de CMV (donneur séropositif/receveur séronégatif). Le rôle potentiel des inhibiteurs de la mTOR dans la prévention de l’infection à CMV chez les transplantés rénaux CMV séropositifs a également été souligné. Chez ces patients, si la mesure de l’immunité spécifique anti-CMV par les techniques Quantiferon-CMV ou l’ELISpot est positive à un mois post-transplantation, la durée de la prophylaxie peut être réduite, tout en continuant une surveillance par biologie moléculaire. Le traitement de l’infection à CMV repose toujours sur le (val)ganciclovir en première intention. Cependant, en cas d’intolérance à ce traitement, le maribavir ou le foscarnet représentent des alternatives de deuxième intention. En cas de CMV résistant/réfractaire, le maribavir est le traitement de première intention, sauf en cas d’atteinte du système nerveux central, de rétinite à CMV ou de virémie élevée. Dans ces cas, le foscarnet doit être préféré. L’utilisation du maribavir en vie réelle en France a montré des résultats identiques à ceux de l’étude pivotale Solstice avec une incidence moindre de résistance au maribavir.

Establishment of Rat Model of Acute Antibody-Mediated Rejection in Kidney Transplantation

Introduction In immunocompromised individuals, particularly organ transplant recipients, the risk of developing Kaposi sarcoma (KS) increases significantly due to prolonged immunosuppressive therapy. The onset of post-transplant KS is highly variable, though most cases occur within the first two years following transplantation. The effectiveness and safety of systemic therapies in the management of post-transplant KS are not well established. In this report, we describe a rare case of early-onset KS in a Tunisian kidney transplant recipient, revealed by deep vein thrombosis just six months after transplantation, and successfully managed with paclitaxel as first-line therapy. Case Presentation We present the case of a 52-year-old Tunisian male who underwent a living-donor kidney transplant in June 2022. Six months after transplantation, the patient presented with deep vein thrombosis, and large purplish plaques were observed on the anterior left thigh. A skin biopsy confirmed the diagnosis of KS. Further investigations revealed systemic involvement. The patient was treated with paclitaxel-based chemotherapy in combination with sirolimus and a reduction in immunosuppressive therapy. As of November 2024, the patient had demonstrated marked clinical improvement, with resolution of KS lesions and stable renal function. Conclusion This case of early-onset Kaposi sarcoma highlights the potential effectiveness of paclitaxel-based chemotherapy combined with sirolimus and a carefully adjusted reduction in immunosuppressive therapy as a promising first-line treatment option.

Commercial high-sensitivity cardiac troponin T (hs-cTnT) assays measure both intact and degraded cTnT forms (i.e. total cTnT) and values are often elevated in chronic kidney disease (CKD) patients. The measurement of long cTnT forms has recently shown improved specificity for acute myocardial infarction compared to total cTnT. However, the associations between long cTnT and adverse long-term outcomes in CKD are unknown. Altogether, 136 CKD stage 4-5 patients not on dialysis were included in this prospective cohort study. Long cTnT and total cTnT levels before dialysis initiation were measured using investigational in-house immunoassays. The associations between cTnT measurements and all-cause mortality, incident major adverse cardiovascular or cerebrovascular events (MACCE), new-onset atrial fibrillation (NOAF) and a composite adverse outcome (all-cause mortality or MACCE) were assessed. Mean age was 61 (±13) years, 47 (34.6%) were female and median values for long cTnT and total cTnT were 1.9 (1.3-3.0) ng/L and 37 (23-66) ng/L, respectively. After a median follow-up of 6.2 (4.6-7.7) years, 62 (45.6%) patients had died, 36 (26.5%) had experienced MACCE, 28 (23.3%) NOAF and 76 (55.9%) a composite adverse outcome. In multivariable Cox models adjusted for age, sex and coronary artery disease (CAD), long cTnT and total cTnT were independently associated with all-cause mortality, NOAF and the composite adverse outcome, while only total cTnT was associated with MACCE. Replacing the adjustment for CAD with kidney transplantation in the multivariable models weakened the significance of the associations. We describe for the first time associations between long cTnT and long-term cardiovascular adverse outcomes and all-cause mortality in a prospective cohort of CKD stage 4-5 patients. https://www. gov NCT04223726. Retrospectively registered in December 10, 2019.

The burden of chronic kidney disease (CKD) is driven by mortality and the necessity of kidney replacement therapy (KRT). CKD causes one death every 20 seconds globally and is among the fastest growing causes of death. It is forecast to become the 5th global cause of death and the 3rd in Western Europe by 2050. It is estimated that 511 549 European Union (EU) inhabitants depend on KRT, with nearly two thirds (≈310 000) treated by dialysis, and the remainder being kidney transplant recipients (≈200 000). KRT is provided by every EU country. France (96 317), Germany (77 900), Spain (67 604) and Italy (62 523) account for 60% of people on KRT in the EU. Prevalence per million population ranged from 560 (Luxembourg) to 2022 (Portugal). Germany (55 129) leads in the number of people on dialysis, followed by France (52 817), Italy (44 382) and Spain (29 879). In addition to differences in the relative number of dialysis and transplant patients, there were also EU-wide differences in modality of dialysis. The hemodialysis/peritoneal dialysis prevalence ratio ranged from 52.0 (Slovakia) to 3.4 (Sweden). The EU should be aware of the burden of KRT when designing regulations, such as the Accelerating Clinical Trials in the EU (ACT EU) and the EU Medical Device Regulation (MDR) or making decisions regarding the prioritization of diseases and the budget for research and healthcare.

Allograft-localized post-transplant lymphoproliferative disorder in a pediatric kidney transplant recipient: a case report and focused review.

Neighborhood Disadvantage and Kidney Transplant Disparities

Unexplained Elevated Cell-Free DNA in a Kidney Transplant Patient With Stable Clinical Parameters: A Case Report and Literature Review.

Background To ensure long term graft and patient survival after kidney transplantation, the correct intake of the immunosuppressive medication is mandatory. To correctly administer the medication, specific knowledge is required. While the significance of adherence has been recognized by many, the potential adverse effects of insufficient knowledge levels—often associated with poor health literacy—have been overlooked for a long time; therefore, little is known about sex-specific differences and other predictors of knowledge in this patient group. Methods We analyzed the longitudinal course of the self-developed and previously successfully applied knowledge test in kidney transplant recipients participating in the KTx360° trial over a period of up to three years. The patients participated in a multidisciplinary aftercare program that included case management, psychosocial assessments and interventions, as well as exercise assessments and interventions, supported by telemedicine. We aimed to identify potential baseline predictors of knowledge trajectories, with a specific focus on sex-specific differences. Results The analysis sample, which consisted of participants with at least one valid measurement on the knowledge test, included 783 adult patients (41.6% women) with a mean age of 52.3 years (SD 13.6). Knowledge levels improved significantly over the period of the KTx360° trial. Especially younger male participants and men not living in a partnership showed an increase in knowledge levels. Conclusions Over the period of the KTx360° trial we observed an increase in knowledge, mainly in patients with below-average baseline knowledge levels. While some improvements might be due to the catch-up effect, other changes suggest a different response to the same stimulus. In sex-specific analyses, we found higher knowledge levels in female participants at the start, but sex did not impact the progression of knowledge levels. Since there was no control group, it is not possible to determine the program's effect on knowledge levels.

Acute rejection (AR) remains a critical challenge to graft survival in kidney transplantation. Although dextrorotatory-amino acids (D-AAs) have been recognized as biologically active compounds, their role in mediating immunosuppression was poorly depicted. To address this, serum samples from renal transplant recipients were analyzed via [d0]/[d5]-estradiol-3-benzoate-17β-chloroformate (17β-EBC) based ion mobility-mass spectrometry (IM-MS) to assess D-AAs levels. scRNA-seq data from the GSE109564 dataset were analyzed. Additionally, murine skin and kidney transplantation models were utilized to assess the in vivo impact of d-kynurenine (D-Kyn) treatment on AR. Through analysis of patient serum and murine transplantation models, we identified D-Kyn as a key metabolite whose elevated levels correlate with stable graft function. We found that D-Kyn, more effectively than its chiral counterpart L-Kyn, inhibits the inflammatory activity of M1 macrophages. This suppression is mediated via the PHGDH/TLR4/Caspase-1 pathway, reducing the transcription and secretion of inflammatory cytokines. In murine models of skin and kidney transplantation, D-Kyn treatment demonstrated potent immunosuppressive effects, attenuating macrophage-mediated inflammation and CD8 + T cell activation, potentially through regulation of macrophage-derived IL-23a. Our findings reveal D-Kyn as a promising therapeutic candidate for preventing acute rejection and improving transplant outcomes and lay the foundation for future clinical applications from the perspective of dextrorotatory amino acids.

Neuroinvasive West Nile Virus Infection in Kidney Transplantation: Three Case Reports.

BK virus infection is a marker of poor immune recovery, especially after kidney or allogeneic cell transplantation. Because of the challenges associated with BK virus infection and the lack of effective treatments, there is a growing interest in novel approaches, such as adoptive cellular therapy, that aim to restore antiviral immunity and promote viral clearance. Our clinical trial assessed the feasibility, safety, and efficacy of administering third-party, BK virus-specific cytotoxic T lymphocytes (CTLs) used to treat allogeneic HCT patients and kidney transplant patients with biopsy-proven BK-virus nephropathy. Comprehensive clinical assessments and correlative studies were performed. The study included six patients after kidney-transplantation and five HCT recipients. Viremia declined in most evaluable patients by Day 45 after BKCTL infusion. No new instances of graft-versus-host disease, kidney-transplant rejection, graft failure, or infusion-related toxicities were attributed to the treatment. Antiviral activity (as assessed by interferon-γ secretion) did not differ between infused BKV-CTLs given to kidney-transplant versus allogeneic SCT recipients. In this study, we longitudinally tracked the in vivo persistence of adoptively transferred BKV-CTLs and demonstrated their sustained functional activity. This therapy could be promising in KT and SCT patients with recent-onset BK-virus viremia.