Search Results (188)

The increasing fragmentation of plastic debris into nanosized particles represents a threat to freshwater ecosystems, yet the biological effects of nanoplastics (NPs) on freshwater invertebrates remain poorly understood. This study investigated tissue distribution, cellular effects and immune responses following acute exposure to polyethylene terephthalate nanoplastics (PET-NPs) in the freshwater gastropod Pomacea canaliculata, a species of high ecological relevance and physiological resilience. Adult snails were injected with PET-NPs at 5 or 10 mg/L and sampled after 24 and 72 h. PET-NPs accumulation in the anterior and posterior kidneys was assessed by fluorescence imaging and tissue morphology was evaluated. Stress- and inflammation-related genes (Pc-Heat Shock Protein (HSP)70, Pc-HSP90 and Pc-Allograft inflammatory factor 1) expression was quantified by RT-qPCR. PET-NPs uptake and phagocytic activity were analyzed in circulating hemocytes in vivo and ex vivo. PET-NPs were accumulated in renal tissues, persisting up to 72 h without histopathological alterations. Gene expression analyses revealed non-linear and dose/time-dependent responses. Hemocytes of different morphologies internalized PET-NPs in a dose-dependent manner and showed intercellular particle transfer. Overall, acute PET-NP exposure determines rapid immune handling and tissue sequestration with limited short-term physiological impact, underscoring the potential involvement of immune processes in NPs fate and highlighting the need for chronic exposure studies. Full article

Background: Renal allograft rejection remains a major challenge in transplantation. Current diagnostic approaches, including biopsies, are invasive and may fail to detect subclinical immune activation, potentially contributing to progressive graft dysfunction. Reliable, non-invasive biomarkers capable of monitoring immune activation and distinguishing rejection phenotypes are therefore needed. Methods: In this retrospective study, we evaluated serum neopterin as a biomarker of immune activation and graft status over 12 months following transplantation. Associations between neopterin levels and immune parameters, including natural killer (NK)-to-CD3⁺CD16/CD56⁺ T cell ratios, cytokines (IFN-γ and IL-10), and CD4⁺CD25⁺FoxP3⁺ T cell frequencies, were assessed. A total of 211 first renal allograft recipients were followed longitudinally, including patients with acute rejection (AR) and matched stable graft (SG) recipients. Serum neopterin was quantified by enzyme immunoassay, and immunophenotyping, mRNA expression, and cytokine profiling were performed on peripheral blood samples. Results: Serum neopterin levels were significantly elevated in AR compared to SG recipients, with a threshold of 57 nmol/L distinguishing AR with 81% sensitivity and 80% specificity. While IFN-γ demonstrated higher diagnostic performance in cross-sectional analysis, neopterin showed a more sustained elevation over time, remaining increased in AR recipients even at later post-transplant time points. Neopterin correlated positively with IFN-γ, but not IL-10, and inversely with CD4⁺CD25⁺FoxP3⁺ T cell frequency. NK cells were enriched during rejection, whereas CD3⁺CD16/CD56⁺ T cells were more prominent in graft stability. The NK-to-CD3⁺CD16/CD56⁺ T cell ratio was highest during acute cellular rejection. Conclusions: Neopterin reflects Th1-associated immune activation in renal allograft recipients and provides a temporally stable, non-invasive marker of immune status. Although it does not outperform IFN-γ levels at the time of rejection, its stability and sustained elevation suggest a complementary role in longitudinal monitoring. Integration of neopterin with immune parameters, including cytokine profiles and cellular subsets, may enhance the assessment of graft immunological status and support clinical decision-making. Full article

Background and Objectives: Renal transplantation is the optimal treatment for end-stage renal disease, yet long-term allograft survival remains threatened by immune-mediated injury and chronic nephropathy. Conventional monitoring using serum creatinine and protocol biopsy suffers from limited sensitivity for early, subclinical injury. Liquid biopsy-based biomarkers offer a non-invasive alternative. Materials and Methods: We conducted a systematic narrative review of studies published between January 2010 and December 2024, identified through PubMed, Scopus, and Web of Science. Results: Extracellular vesicles carry injury-specific molecular cargo reflecting the biological state of tubular, glomerular, and endothelial cells; urinary EV CXCL9 protein and exosomal CD3ε mRNA have demonstrated AUC values of 0.81–0.88 for the detection of T-cell-mediated rejection. Donor-derived cell-free DNA quantifies global graft cell death; the FDA-cleared AlloSure assay achieves an AUC of 0.74 and NPV of 84% at the validated ≥1.0% threshold established in the DART trial. Donor-specific antibodies—particularly complement-fixing C1q-positive DSAs—confer markedly inferior 5-year graft survival compared with DSA-negative recipients (54% versus 93%). Multi-biomarker panels integrating all three modalities yield AUCs of 0.88–0.94 and NPVs of 91–95%. Conclusions: The integration of EV, ddcfDNA, and DSA monitoring into a unified surveillance framework offers a clinically meaningful advance over creatinine-based monitoring. Prospective randomized trials confirming improvement in long-term allograft survival will be the critical next step. Full article

Background and Objectives: Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with adverse graft and patient outcomes. However, its effects on kidney outcomes remain unclear. We retrospectively investigated the association between EAD and various kidney events following LT. Materials and Methods: We included 92 LT recipients. EAD was defined by the presence of ≥1 of the following: total bilirubin level ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level > 2000 U/L within the first 7 days post-LT. Kidney outcomes included acute kidney injury (AKI), acute kidney disease (AKD), kidney replacement therapy (KRT) performance, and changes in estimated glomerular filtration rate (eGFR). Results: AKI incidence was comparable between the non-EAD and EAD groups; however, stage 3 AKI incidence was higher in the EAD group (65.0% vs. 22.2%; p = 0.001). AKD occurred more frequently in the EAD group (75.0% vs. 30.6%, p = 0.001). KRT was required more frequently within 7 days of LT in the EAD group (70.0%) than in the non-EAD group (15.3%) (p < 0.001). Multivariate analysis identified EAD as an independent predictor of KRT requirement (p < 0.001). EAD was associated with prolonged (≥7 days) KRT requirement (p = 0.025). In the receiver operating characteristic curves, all EAD components were associated with KRT requirement following LT. The baseline and 3-month eGFR levels were comparable; however, a trend toward a steeper decline was noted in eGFR in the EAD group than that in the non-EAD group (p = 0.090). The burden of hospitalization and calcineurin inhibitor exposure were similar between the groups. Conclusions: EAD appears to be independently associated with adverse kidney outcomes following LT. Preventive strategies targeting EAD are required to improve post-transplant prognosis and mitigate kidney-related complications. Full article

Rho GTPases are a group of guanosine triphosphate (GTP)-binding proteins with a relative molecular weight of about 20–30 kD, and 22 different Rho GTPases have been identified in mammalian cells, among which RhoA, Rac1 and Cdc42 are the most well-studied. Rho-associated coiled coil forming protein kinase (ROCK) is the most well-researched downstream effector of Rho GTPases. The Rho/ROCK signaling pathway widely participates in the reorganization of the cytoskeleton through cascade phosphorylation/dephosphorylation reactions and modulates cellular biological behaviors including cell adhesion, migration and phenotypic transformation. Abnormal activation of the Rho/ROCK signaling pathway is closely associated with the occurrence and progression of acute kidney injury, diabetic nephropathy, hypertension-related nephropathy and chronic allograft nephropathy, which contributes to podocyte injury, renal tubular epithelial-to-mesenchymal transition (EMT), mesangial cell proliferation and inflammatory infiltration in the kidney. This review focuses on the research progress and regulatory mechanisms of the Rho/ROCK signaling pathway in the above four major kidney diseases and discusses the therapeutic potential of targeting this pathway for kidney disease treatment, aiming to provide new insights for elucidating the pathogenesis of kidney diseases and developing novel therapeutic strategies. Full article

Background: Kidney transplantation is the optimal treatment for end-stage renal disease; however, acute rejection remains a major determinant of long-term graft dysfunction and failure. Donor-derived cell-free DNA (dd-cfDNA) has emerged as a minimally invasive biomarker reflecting allograft injury, with growing evidence supporting diagnostic and prognostic utility. Objectives: This structured narrative review aimed to synthesize contemporary evidence (2020–2025) on the diagnostic and prognostic utility of plasma dd-cfDNA and its integration into kidney transplant rejection surveillance. Methods: A narrative literature review was conducted using PubMed to identify studies published or available online ahead of print, between January 2020 and September 2025, evaluating plasma dd-cfDNA in adult kidney transplant recipients. Manual screening of reference lists supplemented the search. Original clinical studies reporting diagnostic or prognostic outcomes were included, and the results were synthesized narratively due to methodological heterogeneity. Results: Across prospective and retrospective cohorts, elevated dd-cfDNA discriminated rejection from non-rejection biopsies, with strongest performance in antibody-mediated and microvascular rejection phenotypes. Longitudinal studies demonstrated that dd-cfDNA elevations often preceded histologically confirmed rejection and predicted adverse graft outcomes, while low levels were associated with immunologic quiescence. Assay variability limited cross-study comparability, whereas integration with donor-specific antibodies, gene expression profiling, or algorithm-based approaches improved diagnostic and prognostic discrimination. Conclusions: Dd-cfDNA is a clinically meaningful biomarker for kidney transplant rejection monitoring, providing diagnostic and prognostic information beyond conventional functional markers. When interpreted longitudinally and in clinical context, dd-cfDNA supports risk stratification and surveillance, with evidence supporting its expanding role in risk-adapted transplant care. Full article

Background and Objectives: Recurrence of lupus nephritis (LN) after kidney transplantation is a major clinical concern in patients with systemic lupus erythematosus (SLE) who progress to end-stage renal disease (ESRD). Reported rates of post-transplant LN recurrence vary widely and are influenced by patient characteristics, immunosuppressive regimens, and indications for allograft biopsy. Patients and Methods: Medical records of adult LN patients treated at the University Hospital in Kraków, Poland, during the years 2012–2022 were retrospectively reviewed to identify individuals who progressed to ESRD and received a kidney transplant. Data collected included patient demographics as well as clinical, laboratory, transplant-related, and dialysis-related information. Results: Among 1039 patients with SLE, LN was diagnosed in 351 (33.8%), and 28 (8.0%) progressed to ESRD, of whom n = 9 (32.1%) underwent kidney transplantation. All patients received deceased-donor grafts, with a median time from ESRD to transplantation of 3 years (range 1–8) and a median post-transplant follow-up of 6 years (3–20). Maintenance immunosuppression consisted predominantly of glucocorticosteroids, mycophenolate mofetil, and tacrolimus in 77.8% of patients, with basiliximab induction was used in 2 of 2 patients with available data. Biopsy-proven LN recurrence occurred in 22.2% (2/9) of recipients. Graft loss was observed in 22.2% (2/9), while overall mortality reached 33.3% (3/9), including one peri-transplant death and one death due to infectious complications. Hematological manifestations were present in 100% of patients, hypercholesterolemia in 100%, and arterial hypertension in 88.9%, while anti-dsDNA antibodies were detected in 77.8%. LN relapse occurred despite standard immunosuppressive therapy and in the absence of consistent clinical or immunological predictors. Conclusions: LN recurrence occurred in 2 of 9 patients (22.2%). Patients with LN after kidney transplantation require careful long-term monitoring and individualized immunosuppressive management, considering baseline risk profile and relevant clinical with immunological factors. Full article

Kidney transplantation is the optimal treatment for end-stage kidney failure. However, after successful kidney transplantation, patients require long-term immunosuppression. Due to immunosuppressive therapy, the development of malignancies is more common in solid organ transplant recipients than in the general population. Because renal transplantation has been performed for many decades—much longer than other solid organ transplants—data on malignancies in kidney allograft recipients are the most comprehensive. Malignancies are the third most common cause of death in kidney allograft recipients, after cardiovascular disease and infections. In kidney allograft recipients, malignancies may develop de novo, be transmitted with the transplanted organ, or arise from previously present but undiagnosed cancers in the recipient. Over 90% of malignancies in renal allograft recipients are de novo. In this review, we first present the epidemiology of malignancies after kidney transplantation. Subsequently, the most common urinary tract malignancies, along with their diagnosis, treatment, and screening, are discussed. We also outline the limitations of the published data, propose research priorities, and identify existing gaps and unmet needs. Full article

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, and immune activation—including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), β2-microglobulin, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—have emerged as promising alternatives. This study evaluated early post-transplant serum profiles of these biomarkers and their prognostic relevance for long-term graft outcomes. Methods: Nineteen adult recipients undergoing primary kidney transplantation were prospectively enrolled. Serum creatinine and protein biomarkers were measured 24 h post-transplant using validated immunochemical assays. Biomarker concentrations were compared with values from healthy controls, and correlations with renal function at 12 months were assessed. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance. Results: Significant biochemical alterations were observed at 24 h post-transplant. KIM-1 levels were markedly elevated compared with controls (74.50 ± 98.45 vs. 10.54 ± 17.19 ng/mL; p = 0.01), consistent with early tubular injury. IL-1β and NGAL showed upward trends without reaching statistical significance. β2-microglobulin and TNF-α levels did not differ substantially from control values. Serum KIM-1 correlated with serum creatinine both at 24 h (r = 0.35) and at 12 months (r = 0.40). ROC analysis identified a KIM-1 threshold of 24.5 ng/mL (AUC = 0.68) as a potential indicator of future graft dysfunction, outperforming serum creatinine (AUC = 0.64). Six patients experienced graft dysfunction at 12 months post-transplant, five of whom had serum creatinine values > 5 mg/dL at 24 h. Based on early creatinine levels, patients were stratified into low-risk (creatinine < 5 mg/dL; n = 10) and high-risk groups (creatinine > 5 mg/dL; n = 9). Mean KIM-1 concentrations were significantly higher in the high-risk group (110.68 ± 115.29 vs. 26.67 ± 18.05 ng/mL; p = 0.05), consistent with more severe early tubular injury. Conclusions: Among the evaluated biomarkers, KIM-1 demonstrated the strongest potential as an early biochemical indicator of renal allograft dysfunction. Its rapid post-transplant elevation underscores its sensitivity to early tubular injury. Further prospective validation in larger, multicenter cohorts is warranted. Full article

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance. Full article

Background and Clinical Significance: Kidney transplant recipients have a 2–4-fold higher cancer risk than the general population. The sequential occurrence of multiple myeloma (MM) and native-kidney renal cell carcinoma (RCC) is rare and creates competing priorities between anti-myeloma efficacy and allograft preservation. Case Presentation: A 54-year-old woman with a 2020 living-donor kidney transplant presented in 2024 with bone pain and shoulder swelling. Low-dose whole-body CT showed multiple punched-out osteolytic lesions. Work-up revealed IgG-κ M-protein 38.5 g/L and 25% clonal plasma cells; cytogenetics showed a complex karyotype (R-ISS III). First-line bortezomib/cyclophosphamide/dexamethasone (VCd) was given while maintaining tacrolimus plus low-dose steroid. After four cycles, she achieved very good partial response (M-protein 42.3 to 5.6 g/L) with stable graft function. Follow-up imaging detected a large exophytic mass in the native right kidney; nephrectomy confirmed papillary RCC, type II. Later, the myeloma progressed with epidural extension causing cord compression. Second-line daratumumab/carfilzomib/dexamethasone (DKd) and palliative spine radiotherapy were initiated. The course was complicated by opportunistic infection and pancytopenia, and the patient died in January 2025. Conclusions: Vigilant post-transplant cancer surveillance—including native-kidney RCC—tailored immunosuppression, and multidisciplinary coordination are critical. VCd with tacrolimus may be feasible when graft preservation is prioritized; however, relapsed high-risk MM on DKd carries substantial infectious risk and a guarded prognosis. Full article

Objective: The aim was to characterize the real-world use of GLP-1 receptor agonists (GLP-1 RAs) and/or SGLT2 inhibitors in kidney transplant recipients (KTRs) with diabetes and to compare the clinical management, safety, and effectiveness between patients with type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM). Methods: This retrospective longitudinal cohort study included 141 adult KTRs (T2DM: 52; PTDM: 89) who initiated GLP-1 RA and/or SGLT2 inhibitor (SGLT2i) therapy between August 2013 and April 2024. Metabolic control, medication use, and safety outcomes were assessed from baseline to end follow-up, with a mean treatment exposure of 2.4 years. Results: Overall, 69% were treated with an SGLT2i and 59% with a GLP-1 RA; because the groups were not mutually exclusive, 28% received both agents. Treatment was associated with significant reductions in body weight (−3.38 kg; p < 0.001) and BMI (−1.28 kg/m²; p < 0.001) in both subgroups. HbA1c showed a non-significant overall decline (−0.31%; p = 0.21), with a greater reduction in the T2DM subgroup (−0.50%; p < 0.01). Significant improvements were also observed in lipid profile and blood pressure. Renal allograft function remained stable in both groups. The overall safety profile of the therapies was favorable, with mild urinary tract infections (18%) and manageable nausea (6%) reported in the entire cohort. No episodes of acute rejection or severe hypoglycemia occurred during the study period. Conclusions: In real-world practice, GLP-1 RAs and SGLT2is were associated with improved cardiometabolic parameters and stable renal function in KTRs, with a manageable safety profile. Similar effectiveness and safety across T2DM and PTDM support the use of these agents throughout the spectrum of diabetes in transplant recipients. Full article

Background: Switching stable liver transplant (LT) recipients from twice-daily immediate-release tacrolimus (IR-Tac) to once-daily MeltDose^® extended-release tacrolimus (LCPT) has been proven safe and well tolerated. Moreover, the switch has been associated with enhanced treatment adherence, improvement of tremors, and preserved renal function. Here, we hypothesized that switching to LCPT early after LT may enhance long-term patient outcomes significantly. Methods: This single-center, observational study investigated the long-term safety of LCPT in a large cohort of LT recipients (n = 100). Allograft function, emerging adverse events, the incidence of rejection reactions, renal function, lipid and glucose metabolism, and treatment adherence were assessed over 24 months. Results: In 56% of patients, the switch was conducted within 4 weeks post-transplantation. Adverse events occurred in 90% of patients during the 24-month follow-up, including gastrointestinal complications (28%), neurological symptoms (28%), skin disorders (26%), metabolic disorders (22%), and fatigue (18%). Seven patients (7%) developed renal insufficiency, and five patients (5%) developed renal failure. Three episodes of chronic graft rejection reactions (3%) and a single transplant failure (1%) were observed over 24 months. LCPT was discontinued in 10 patients. Liver and renal function markers, blood lipids (cholesterol and triglycerides), and glucose levels remained stable over the 24-month follow-up. However, 58% of LT recipients had one of their liver function markers elevated at baseline (i.e., before the switch), 28% had low glomerular filtration rate (GFR < 60 mL/min/1.73 m²), and 18% had high serum creatinine (>1.3 mg/dL). In these subgroups, the early switch to LCPT was associated with a significant decrease in liver enzymes (p < 0.001 for alanine transaminase; p = 0.032 for gamma-glutamyl transferase; and p < 0.001 for total bilirubin) and a significant decrease in serum creatinine levels (p < 0.001). Self-reported treatment adherence was good and consistent throughout the study. Conclusions: The early switch from IR-Tac to LCPT was safe and effective in our cohort and may be particularly beneficial for patients with suboptimal liver and renal function following LT. Full article

Peritubular capillaritis (ptc) is a hallmark lesion of antibody-mediated rejection (AMR), but the grading of its extent is historically based on arbitrary defined cut-offs. Molecular AMR diagnosis via intragraft gene expression measurements may provide evidence to challenge established ptc categories. We retrospectively included 38 renal allograft biopsies from clinical routine, performed because of suspicion of AMR. Biopsies were re-assessed by an experienced nephropathologist and intragraft gene expression was measured using the NanoString nCounter^® platform. Ptc categories were correlated with AMR gene expression to identify a ptc extent cut-off with optimal prediction of molecular diagnosis of AMR [gene expression levels above first quartile (AMR^Q>1)]. Finally, an independent validation cohort (n = 25, Erasmus MC, Rotterdam, The Netherlands) was included to reproduce the results. Re-assessment of biopsies revealed AMR in 26/68.4%, mixed rejection in 5/13.2%, and T-cell-mediated rejection in 3/7.9%. Biopsies with diffuse ptc had significantly higher AMR gene expression compared to biopsies with focal ptc and biopsies with no ptc (64.0/53.3–84.0 vs. 31.5/27.0–49.5, p = 0.023 and 27.0/14.3–31.8, p = 0.003, median/IQR). Sensitivity analysis revealed that a ≥35% ptc cut-off resulted in higher AUCs for predicting AMR^Q>1 compared to ptc^50% (AUC 0.78, 95% CI: 0.63–0.93, p = 0.009 versus AUC: 0.74, CI: 0.56–0.90, p = 0.03). In the validation cohort, only the ptc^35–, but not the ptc^50%, cut-off significantly predicted AMR^Q>1 (AUC 0.75, 95% CI: 0.54–0.96 p = 0.04 vs. AUC 0.69, CI: 0.46–0.93, p = 0.13). Using intragraft gene expression measurement, we identified a new ptc extent threshold with better prediction of molecular AMR. The newly proposed cut-off of ≥35% could potentially improve diagnostic evaluation and prognostication in cases with suspected or diagnosed AMR. Full article

Rabbit antithymocyte globulin is one of the most commonly used agents for induction immunosuppression in renal transplantation. It has contributed significantly to improved allograft survival and has a favorable safety profile. Despite its advantages, rabbit antithymocyte globulin carries a rare but potentially life-threatening risk of anaphylaxis, which can lead to severe morbidity and mortality. Anaphylaxis is an acute and dramatic complication that requires prompt recognition and immediate management. In this review, we discuss the pathophysiology, clinical features, and management of rabbit antithymocyte globulin-associated anaphylaxis. We have also included practical insights from our clinical experience to guide early recognition and management, aiming to help clinicians safely manage this critical adverse event. Full article