Search Results (2,550)

Background/Objectives: Urinary tract infections (UTIs) represent the most common infectious complication following kidney transplantation. An increasing number of UTIs are caused by multidrug-resistant organisms (MDROs). The role of intestinal MDRO colonisation in complicated urinary tract infections (cUTIs) among kidney transplant recipients is not fully understood. Methods: We conducted a retrospective, single-centre study of kidney or kidney–pancreas transplant recipients hospitalised for infectious diseases. Each hospitalisation was analysed as a separate event. Routine rectal screening targeted carbapenem-resistant Enterobacterales and vancomycin-resistant/vancomycin-variable enterococci. Results: The study included 65 hospitalisations from 52 kidney transplant recipients, with some patients contributing multiple admissions. cUTIs accounted for 63.1% of admissions, and 22.0% of cUTIs were associated with concomitant bloodstream infection (BSI). The most frequently isolated pathogens were Klebsiella pneumoniae (58.8%) and Escherichia coli (41.2%). Extended-spectrum β-lactamase (ESBL) production was detected in 50% of E. coli isolates, while carbapenemase production was identified in 60% of K. pneumoniae isolates. MDRO rectal carriage was detected in 43.1% of cases and was more frequent in cUTI than in other infections (53.7% vs. 25.0%, p = 0.024). Carbapenemase-producing K. pneumoniae (CP-KP) rectal carriage was also more frequent in cUTI (31.7% vs. 4.2%, p = 0.011), but did not remain statistically significant after adjustment for urinary stent presence (odds ratio 7.1, 95% CI 0.7–66.2; p = 0.087). Nevertheless, CP-KP rectal carriage was associated with CP-KP cUTI aetiology (PPV 75.0%; NPV 86.4%). The median length of hospital stay (LoS) was 15 days. In multivariable analysis, a longer median LoS was associated with BSI (12.2 days; 95% CI: 0.8–23.6; p = 0.037), urinary stent presence (6.8 days; 95% CI: 1.5–12.2; p = 0.014), and older age (2.3 days; 95% CI: 0.7–4.0; p = 0.007). Conclusions: Rectal CP-KP colonisation may represent a potential marker of cUTI risk, although its independent association was not confirmed after adjustment. These findings should be interpreted with caution, given the study design and sample size and require confirmation in larger prospective studies. Rectal screening may contribute to early risk stratification, whereas its role in guiding empirical therapy remains to be prospectively evaluated. Full article

Background: De novo donor-specific antibodies (dnDSA) are associated with impaired allograft outcomes and the development of acute and chronic antibody-mediated rejection. However, their clinical impact during the early post-transplant period remains incompletely characterized. Methods: In this prospective single-center cohort study, we analyzed 218 kidney transplant recipients between 2006 and 2013 All patients underwent serial screening for the development of de novo donor-specific antibodies at different time points (1, 3, 6, 12 months) after kidney transplantation using contemporaneously available ELISA- or Luminex-based solid-phase assays. The data were correlated with clinical parameters and histopathological results from indication biopsies and analyzed in relation to clinical outcomes and histopathological findings. All data were analyzed to assess the impact on 1-year kidney function, patient and graft survival. Results: One year after renal transplantation, 7% of patients (n = 37) developed de novo donor-specific antibodies (dnDSA). Among dnDSA-positive patients, 22% developed class I dnDSA, 67% class II dnDSA, and 11% both. In univariate analysis, markers of increased immunologic risk—such as previous transplantation, greater HLA mismatch, and reductions in immunosuppressive therapy—were associated with an increased risk of de novo donor-specific antibody (dnDSA) development. However, in multivariate analysis, only a panel-reactive antibody (PRA) level greater than 20% emerged as an independent predictor of dnDSA formation. Patients who developed dnDSA experienced a significant decline in graft function, with an approximately fourfold increased risk of overall graft failure within the first year. DnDSA-positive patients showed significantly reduced graft survival and impaired renal function at one year. Rejection rates were significantly higher in this group, with 48.6% experiencing histologically confirmed rejection, compared to 13.3% among dnDSA-negative patients. Conclusions: Monitoring for de novo DSA after kidney transplantation helps to identify patients at high risk for rejection, declining graft function, and poorer long-term outcomes. Routine post-transplant dnDSA monitoring may support early risk stratification and individualized clinical management. Full article

The rising prevalence of chronic kidney disease represents a major global health burden. Limitations of current renal replacement therapies, including donor organ shortages, rejection, and dialysis-related complications, underscore the need for innovative treatment options. This narrative review assesses the feasibility of bioengineered kidneys as an alternative to current treatments by discussing advances in decellularization, recellularization, and the transplantation of cell-on-scaffold kidneys. We propose that the development of functional bioengineered kidneys follows a hierarchical, staged process, in which vascular patency is the primary prerequisite for graft survival, followed by partial restoration of glomerular filtration, with complete tubular function remaining the final and most challenging milestone. Perfusion-based whole-organ decellularization has made significant progress in preserving the extracellular matrix, enabling the production of acellular human kidney scaffolds. However, complete recellularization of whole kidneys has not yet been achieved. Nevertheless, partially repopulated kidney scaffolds have been shown to withstand physiological blood pressure, produce urine, and exhibit filtration in large-animal models. Complete endothelial coverage of the vascular network proved essential for preventing thrombosis after transplantation. Current work on bioengineered kidneys shows promising results regarding feasibility for clinical application. It is important to note that most of the included studies are proof-of-concept, characterized by small sample sizes and short observation periods. Although these findings are crucial for further research, they cannot be generalized, and larger trials are recommended. In addition to cell-on-scaffold kidneys, 3D bioprinting is a promising technique that could eliminate the need for donor scaffolds. Full article

Background/Objectives: In the United States, HF prevalence is projected to progressively rise by 2030. Prior research suggests a strong association between reduced sleep duration and increased cardiovascular disease and HF risk. This study introduces an alternative parameter, the weekend sleep recovery (WSR), measured by the weekend-to-weekday sleep duration ratio (SDR), to evaluate its association with HF risk. Methods: We conducted a cross-sectional analysis of NHANES (National Health and Nutrition Examination Survey) 2017–2023 to examine self-reported sleep patterns. Participants were classified as WSR (SDR > 1) or non-WSR (SDR ≤ 1). Multivariate logistic regression assessed the association between WSR and HF, adjusting for demographics and comorbidities. Results: Among 8320 participants included in the fully adjusted analysis, WSR was associated with lower odds of HF compared with non-WSR (adjusted OR 0.73, 95% CI 0.55–0.96; p = 0.026). A significant interaction was observed between WSR and weekday sleep duration (P for interaction = 0.003), whereas no interaction was found with weekend sleep duration. In exploratory subgroup analyses, nominally significant associations were observed in several clinical subgroups; however, after correction for multiple comparisons, only participants without dyslipidemia retained statistical significance. No significant effect modification by race/ethnicity was observed (P for interaction = 0.436). Conclusions: Weekend sleep recovery was associated with lower odds of HF in this cross-sectional study. The association varied according to weekday sleep duration but was generally consistent across racial/ethnic groups. Given the observational design, these findings should be interpreted as associative rather than causal and warrant confirmation in prospective studies. Full article

Background: Rejection remains a major barrier to long-term kidney allograft survival, and pre-transplant risk stratification remains incomplete. This study evaluated whether pre-transplant serum Fourier-transform infrared (FTIR) spectra, analyzed using machine learning methods, could identify kidney transplant recipients at increased risk of subsequent biopsy-proven rejection. Methods: In this retrospective single-center study, 80 pre-transplant serum samples collected on the day of transplantation were initially evaluated; after spectral quality control, 79 samples were retained for analysis. FTIR spectra were acquired in transmission mode and analyzed in the 600–1900 cm⁻¹ and 2800–3400 cm⁻¹ regions. Multiple preprocessing strategies were assessed, including Rubber Band baseline correction, vector normalization, and first- and second-derivative transformation, with and without normalization. Naïve Bayes classifiers with Leave-One-Out Cross-Validation and Fast Correlation-Based Filter feature selection were applied. Results: Exploratory analysis showed broad overlap between groups, indicating a subtle multivariate spectral signal. In the initial exploratory workflow, classifier performance depended strongly on preprocessing and feature selection. Because non-nested feature selection may produce optimistic estimates, the main supervised analysis was repeated using FCBF nested within each LOOCV training fold. The best-performing nested model was obtained using second derivative transformation followed by normalization in the combined 600–1900 and 2800–3400 cm⁻¹ regions, achieving an AUC of 0.837, accuracy of 0.747, sensitivity of 0.675, specificity of 0.821, balanced accuracy of 0.748, and F1-score of 0.730. Permutation testing with 1000 label-randomized repetitions supported performance above chance expectation, with no permuted model reaching the observed AUC (empirical p = 0.000999). Conclusions: Pre-transplant serum FTIR spectroscopy combined with leakage-aware nested machine learning analysis identified an internally validated spectral signal associated with subsequent biopsy-proven rejection. These findings support FTIR as a promising complementary and hypothesis-generating approach for pre-transplant biochemical risk phenotyping, requiring external multicenter validation before clinical application. Full article

The role of gut microbiota and intestinal dysbiosis in promoting inflammaging in chronic kidney disease (CKD) has been the focus of intense research over the last years. Some alterations at the phyla level, such as abundance of Proteobacteria and reduction in Firmicutes/Bacteroidites (F/B) ratio and saccarolytic populations, have been consistently reported in CKD. Other mechanisms include microbial translocation through a “leaky gut” and subsequent molecular mimicry, immune dysregulation (unbalance between T reg and Th17 subsets), and epigenetic interactions. Alterations of metabolic pathways and of bacterial metabolites, such as butyrate and other short chain fatty acids (SCFA), also appear to play a key role in modulating progression of CKD. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, synbiotics, postbiotics and fecal microbiota transplantation (FMT). Modulation of microbiota could correct critical alterations, such as F/B ratio and T reg/Th17 unbalance, blunting inflammaging and potentially reducing progression of CKD and cardiovascular disease. Despite current limitations, gut microbiota is emerging as a powerful environmental factor which could be harnessed to interfere with key mechanisms leading to inflammaging in CKD. Full article

Background: During the COVID-19 pandemic, uncertainty regarding the safety of kidneys from COVID-19-positive donors led to a reduction in kidney transplants and increased organ non-use in the United States. This study aims to evaluate whether donor COVID-19 positivity is associated with one-year post-transplant estimated glomerular filtration rate (eGFR) among kidney transplant recipients. Methods: This retrospective cohort study used data from the United States Organ Procurement and Transplantation Network (OPTN) 2020–2024. Donor COVID-19 status was determined by the SARS-CoV-2 nucleic acid amplification technique (NAT) and antibody test results. The main outcome was recipients’ one-year eGFR, estimated by the CKD-EPI 2021 formula. Linear regression models were used to compare the mean one-year eGFR among donor COVID-19 groups, adjusted by inverse probability of treatment weights. Interaction terms of donor acute kidney injury status and race were assessed to evaluate effect modification. Results: Among 38,199 included kidney transplant recipients, 1090 (2.9%) received kidneys from donors with active COVID-19 infection, 423 (1.1%) from donors with resolved infection, and 36,686 (96.0%) from COVID-19-negative donors. After weighting and adjustment, there was no significant difference in one-year eGFR for recipients of kidneys from donors with active COVID-19 (mean difference, 0.05 [95% CI, −1.08 to 1.18]) or resolved infection (mean difference, −0.27 [95% CI, −2.19 to 1.64]) compared with COVID-19-negative donors. Neither donor AKI nor donor race modified the association between donor COVID-19 status and one-year eGFR. Conclusions: This study suggests that kidneys from COVID-19-positive donors may be a viable option without compromising short-term allograft function as measured by 1-year eGFR. Full article

Background/Objectives: Chronic kidney disease (CKD) is associated with numerous oral manifestations that may negatively affect quality of life, nutrition, and overall health. This narrative review aimed to summarize current evidence regarding oral manifestations of CKD and kidney transplantation, examine their proposed underlying mechanisms, and discuss implications for dental management. Methods: A structured literature search of PubMed/MEDLINE was conducted for English-language publications from January 2000 to March 2026. Original studies, systematic reviews, meta-analyses, clinical guidelines, and relevant narrative reviews were included. Additional references were identified through manual screening of bibliographies. Results: Oral manifestations associated with CKD include xerostomia, periodontal disease, oral infections, anemia-related mucosal pallor, developmental enamel defects, and medication-related gingival overgrowth. Kidney transplant recipients are additionally at risk of opportunistic infections and oral malignancies related to long-term immunosuppressive therapy. While oral diseases, particularly periodontal disease and oral infections, may contribute to systemic inflammation, much of the available evidence remains observational. Similarly, many recommendations for dental management are based on expert consensus and clinical experience rather than high-quality interventional studies. Conclusions: Oral complications are common throughout the CKD continuum and warrant regular assessment and preventive care. Multidisciplinary collaboration is essential, while further prospective studies are needed to strengthen the evidence base for clinical management. Full article

Background: The 2022 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest the use of Renin–angiotensin–aldosterone system inhibitors (RAASIs) in chronic Kidney Disease (CKD) stages IV–V, in contrast to the 2012 KDIGO guidelines, which discouraged it. This study aims to assess the impact of RAASIs on kalemia and mortality in a large sample of dialysis patients, where longitudinal data remain scarce, comparing traditional statistical methods with machine learning (ML) algorithms. Methods: This observational longitudinal analysis included 4764 hemodialysis (HD) patients from the Sicilian Registry of Nephrology, Dialysis and Transplantation, with a total of 56,964 longitudinal measurements. We evaluated the impact of RAASIs on serum potassium levels and all-cause mortality in the dialysis setting, comparing traditional statistics and ML. Linear Mixed Models (LMM) and Cox models with mixed effects were used for longitudinal and survival analyses. These were compared with ML approaches, including Random Forest (RF) for potassium variability and Lasso-regularized models for mortality, using four-fold cross-validation. Results: The study included 4764 patients, of whom 1207 (25%) were treated with RAASis. The mean age was 66 ± 15 years, 62% were male, 33% were diabetic, and a history of arterial hypertension was reported in 74% of patients. Hyperkalaemia at baseline was present in 1848 patients. The longitudinal model showed a statistically significant increase in kalemia [adjβ = 0.10 mmol/L, 95%CI 0.05/0.15, p < 0.001], but it was clinically negligible. Indeed, RF did not detect RAASIS as a relevant variable. Association between RAASIs and mortality was not detected either with Cox or ML models. Furthermore, the RF model outperformed traditional LMMs in explaining total potassium variability (56% vs. 43%). Conclusions: RAASI therapy in HD patients is associated with a minimal, non-clinically significant increase in serum potassium and does not impact all-cause mortality. The integration of ML reinforces the robustness of these findings, supporting the safety of RAASIs in the dialysis setting. Full article

Pediatric acute liver failure (PALF) is a rare but life-threatening condition characterized by rapid clinical deterioration and high mortality. Viral infections represent a major etiology of PALF, although the causative agent remains unidentified in a substantial proportion of cases. Human Enteroviruses (EVs) are typically associated with self-limiting illnesses; however, they may rarely cause severe systemic disease, including fulminant hepatitis, particularly in neonates and young children. We describe the case of a 4-year-old previously healthy male who presented with acute fulminant hepatitis secondary to systemic Echovirus 25 (E25) infection, with concomitant Epstein–Barr virus (EBV) co-infection of recent onset. The diagnosis was established through multiplex PCR on cerebrospinal fluid, blood, stool, and nasopharyngeal aspirate, with serotype confirmation by the Italian National Institute of Health. The patient required intensive supportive care including therapeutic plasma exchange (TPE), continuous kidney replacement therapy (CKRT), and intravenous immunoglobulins (IGIV). Despite initial clinical deterioration and placement on the liver transplant list, the patient achieved complete hepatic recovery and was discharged after fourteen days of hospitalization without requiring transplantation. This case highlights the importance of prompt virological workup including enterovirus PCR in children presenting with acute liver failure of undetermined etiology and supports the use of extracorporeal therapies as a bridge to recovery. Full article

Background: Simultaneous pancreas–kidney (SPK) transplantation can restore renal function and insulin independence, but non-technical pancreas graft dysfunction remains difficult to anticipate. Methods: We conducted an exploratory single-centre retrospective biomarker-modelling study to determine whether day-zero recipient serum Fourier-transform infrared (FTIR) spectra are associated with subsequent loss of insulin independence after SPK transplantation. Results: Among 104 screened recipients, 51 met predefined sample-availability, spectral-quality, data-linkage and endpoint-adjudication criteria; 30 maintained pancreas graft function and 21 developed dysfunction. Cases dominated by early technical surgical failure were excluded. Clinical-only, FTIR-only and FTIR–clinical Naïve Bayes models were evaluated using leave-one-out cross-validation with Fast Correlation-Based Filter feature selection. In locked-feature internal validation, the best FTIR-only model used second-derivative spectra with vector normalization and nine selected wavenumbers, achieving AUC 0.997 (95% CI 0.985–1.000) and accuracy 0.961 (95% CI 0.902–1.000). A fixed-feature permutation analysis exceeded label-randomized performance (empirical p = 0.001). The secondary Group 1 versus Group 3 analysis suggested discrimination of pancreas dysfunction despite preserved kidney function (AUC 0.992; accuracy 0.930). Conclusions: Given the small cohort, high-dimensional input, non-nested feature selection, selection-bias risk and absence of external validation, serum FTIR should be considered a candidate risk-enrichment platform requiring prospective multicentre validation. Full article

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75% of renal cell carcinomas and is defined by near-universal VHL inactivation, leading to constitutive HIF stabilisation, metabolic reprogramming, and an immunologically distinct tumour microenvironment (TME). Although ccRCC is characterised by abundant immune infiltration, this paradoxically correlates with poor prognosis, reflecting a TME that imposes interconnected physical, immunological, and metabolic barriers to effective immunotherapy. Chimeric antigen receptor (CAR)-based therapies have revolutionised the treatment of haematological malignancies, but their translation to ccRCC has encountered substantial hurdles. The first-in-human trial targeting carbonic anhydrase IX (CAIX) was limited by on-target off-tumour toxicity and CAR immunogenicity—lessons that fundamentally reshaped the field. CD70 has since emerged as the dominant clinical target, expressed in over 80% of ccRCCs with a highly restricted normal tissue distribution. The phase I COBALT-RCC trial of CTX130, an allogeneic CRISPR-Cas9-edited CD70-directed CAR-T cell product, provided formal proof of concept, achieving disease control in 81.3% of heavily pretreated patients and a durable complete response now exceeding three years—the first such sustained remission reported for any CAR-T cell product in a solid malignancy. Nevertheless, the low frequency of durable responses and universal loss of CAR-T cell persistence by day 28 underscore that major barriers remain. Beyond CD70, the field has diversified across multiple platforms, including CAR–natural killer (NK) cells, CAR–natural killer T (NKT) cells, and CAR–macrophages, each offering distinct biological advantages. This review synthesises current knowledge of the ccRCC TME, the preclinical landscape of CAR-based therapies, and emerging clinical evidence from more than 30 registered trials. We discuss target antigens; engineering strategies to overcome TME barriers, including cytokine armouring, chemokine receptor co-expression, switch receptors, and metabolic reprogramming; and rational combination approaches. We argue that the convergence of optimised target selection, cellular engineering, combination strategies, and biomarker-driven trial design may ultimately improve outcomes for patients with ccRCC. However, achieving a cure remains an aspirational goal, and significant barriers must first be overcome. Full article

Background: Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), but long-term outcomes remain limited by chronic allograft injury, infections, metabolic complications, and cardiovascular risk. Gut microbiota alterations and microbiota-derived metabolites may influence immune regulation, inflammation, drug metabolism, and graft outcomes through the gut–kidney axis. This review summarizes evidence on the gut microbiota in kidney transplantation, emphasizing immune tolerance, complications, cardiovascular risk, graft function, and perspectives. Methods: A structured search was conducted in PubMed, Scopus, and Web of Science to May 2026. Eligible publications included studies involving kidney transplant recipients (KTR), kidney disease or solid organ transplant populations, and mechanistic models. Evidence was synthesized narratively. Results: Gut microbiota alterations in KTR reflect pre-transplant dysbiosis and post-transplant exposures, including antibiotics, immunosuppression, infection, diet, hospitalization, and graft function. Dietary factors and nutrient-derived substrates may modulate microbial composition and production of relevant metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), tryptophan-derived compounds, bile acid derivatives, and uremic toxins. Microbiota-related pathways may involve barrier dysfunction, microbial translocation, innate immune activation, altered regulatory T cell/T helper 17 (Treg/Th17) balance, metabolite signaling, uremic toxin generation, and endothelial stress. Clinical studies associate dysbiosis and microbial metabolites with diarrhea, infections, delayed graft function (DGF), rejection-related shifts, tacrolimus variability, cardiovascular risk, graft dysfunction, graft failure, and mortality. Most findings need validation. Conclusions: Gut microbiota signatures and microbial metabolites are promising markers of transplant-related risk, but not established causal determinants or therapeutic targets. Clinical translation requires standardized methods, multi-omics integration, and prospective patient- and graft-centered trials. Full article

Membranous nephropathy (MN) and minimal change disease (MCD) are the most common causes of nephrotic syndrome following hematopoietic stem cell transplantation (HSCT), a complication conventionally attributed to chronic graft-versus-host disease (GVHD). Paraneoplastic MCD is well described in lymphoid malignancies but is rarely reported in myeloid neoplasms. We report two cases of biopsy-confirmed MCD presenting as the initial manifestation of acute myeloid leukemia (AML) relapse following allogeneic HSCT. Both patients were White men in their sixties with relapsed/refractory AML who developed nephrotic-range proteinuria and acute kidney injury after matched unrelated donor HSCT without histologic evidence of GVHD. Renal biopsies confirmed MCD in both cases. Corticosteroid therapy was ineffective in halting renal deterioration; renal function improved only after initiation of leukemia-directed therapy, with one patient achieving dialysis independence. These cases highlight a rare paraneoplastic presentation of AML relapse. Nephrotic syndrome due to MCD may signal post-HSCT leukemia recurrence, and evaluation for AML relapse warrants consideration in steroid-refractory cases or those without concurrent GVHD. In such cases, control of the underlying malignancy, rather than escalation of immunosuppression, may be central to renal recovery. Full article

Organ failure remains one of the foremost medical and socioeconomic challenges of the twenty-first century, with global transplant waiting lists far exceeding the supply of donor organs. Chronic supportive therapies sustain life but do not restore organ function, underscoring an urgent need for curative alternatives. Bioartificial organs represent a major frontier in organ replacement, driven by converging advances in cell biology, biomaterials science, and bioengineering. By integrating living cells or biologically derived matrices with engineered devices or scaffolds, these systems aim to restore functions that purely mechanical supports cannot reproduce. This review examines the principal technological platforms underpinning the field, including cell encapsulation, decellularization and recellularization, three-dimensional bioprinting, organoids, organ-on-chip systems, and xenotransplantation, and discusses their application to kidney, liver, heart, pancreas, and lung replacement. Across organ systems, progress is advancing from experimental proof-of-concept toward modular and increasingly translational platforms, although whole-organ bioengineering remains largely preclinical for the most structurally complex targets. The major unresolved barriers include vascularization, immune compatibility, scalable cell manufacturing, durable function, and stable integration between biological and engineered components. Overall, bioartificial organ engineering is evolving toward clinically relevant therapeutic strategies capable of complementing, bridging, or eventually reducing dependence on donor-organ transplantation. Full article