Search Results (2,306)

Background and Clinical Significance: COVID-19 may worsen in patients receiving immunosuppressants. Furthermore, drug–drug interactions and concomitant use of anti-inflammatory drugs complicate treatment. We report the clinical course of severe COVID-19 pneumonia in a 74-year-old Japanese male kidney transplant recipient. Case Presentation: The patient had been taking tacrolimus (TAC) (2.5 mg/day), mycophenolate mofetil (1000 mg/day), and prednisone (5 mg/day) since his kidney transplant 7 years earlier. Twenty days before admission, he tested positive for SARS-CoV-2 antigen and was administered molnupiravir for 5 days. At admission, real-time PCR testing of a nasopharyngeal specimen revealed high viral loads, with Ct values of 22.2 and 27.9 for the E and N2 genes, respectively. An oxygen flow rate of 15 L/min was required to maintain arterial oxygen saturation above 90%. TAC was continued, and antibiotics, steroids, anti-interleukin-6 receptor antibodies, intravenous immunoglobulin, and ensitrelvir (ESV) were administered. With invasive positive-pressure ventilation, positive end-expiratory pressure (PEEP), and prone positioning, the arterial oxygen tension/inspired oxygen tension (P/F) improved from 61.3 to 386 within 7 h. The patient was extubated 30 h after admission. The TAC dose was adjusted from 2.5 mg/day to 1 mg/day to achieve the target trough level. The patient was discharged on hospital day 8. PCR testing at discharge showed a decrease in viral load. Conclusions: This study provides insights into the treatment of COVID-19 in patients receiving immunosuppressants. Combination therapy of ESV and TAC was feasible in kidney transplant recipients with dose adjustment. The use of other anti-inflammatory drugs should also be considered. Full article

Background: Pregnancy following liver and kidney transplantation is rare. The presence of a rare genetic disorder and advanced chronic kidney disease (CKD) further complicates clinical management, for which evidence-based guidelines are limited. Case presentation: A 29-year-old woman with Alagille syndrome underwent combined liver and kidney transplantation in early childhood. She had stage 4 CKD, and her baseline creatinine was around 250 umol/L. Her pregnancy was unplanned and diagnosed at 19+1 weeks of gestation. After the diagnosis of pregnancy, immunosuppressive therapy was promptly adjusted, and potentially teratogenic medications were discontinued. At 21+1 weeks’ gestation, creatinine and urea levels rose despite multidisciplinary management, and she started renal replacement therapy. Despite ongoing multidisciplinary care, the pregnancy was complicated by placental abruption at 24+5 weeks, requiring a preterm cesarean section. A live-born female infant weighing 590 g was delivered. Discussion: The coexistence of CKD, long-term immunosuppression, and high obstetric risk requires early multidisciplinary assessment and individualized management. Currently, standardized protocols for monitoring and treatment are lacking in this rare population, making clinical decision-making particularly challenging, especially regarding CKD progression. Conclusion: Pregnancy in women with combined liver and kidney transplantation and advanced CKD carries a high risk of severe renal and obstetric complications. Preconception counseling and early referral to multidisciplinary teams may help improve management in similar rare clinical scenarios. Full article

Background/Objectives: Hepatitis B virus (HBV) transmission risk from donors with resolved HBV infection remains a concern in kidney transplantation, because covalently closed circular deoxyribonucleic acid (DNA) may persist despite serological recovery. In this study, we evaluated the transmission risk from anti-hepatitis B core antibody (anti-HBc)-positive, hepatitis B surface antigen (HBsAg)-negative, and HBV-DNA-negative living donors to anti-HBc-negative recipients. Methods: We retrospectively reviewed living-donor kidney transplantations performed at our institution (June 2011–December 2024). Among 277 transplantations, 26 met the inclusion criteria. All recipients had received HBV vaccination prior to transplantation. Serological markers, including HBsAg, anti-HBc, anti-hepatitis B surface antibody (anti-HBs), and HBV-DNA, were monitored before and after transplantation. Results: Five recipients (19.2%) achieved anti-HBs seroconversion after vaccination pre-transplantation, but all lost protective antibody levels before or shortly after transplantation. Five recipients (19.2%) showed transient post-transplantation anti-HBs positivity; three cases were considered vaccine-related, and two were possibly transplant-related. None of the patients developed liver enzyme elevation, clinical hepatitis, HBsAg positivity, or anti-HBc seroconversion. Among the four recipients tested for HBV-DNA, all results remained undetectable throughout follow-up. None of the recipients maintained protective anti-HBs levels pre- or post-transplantation, despite universal vaccination. Two recipients (7.7%) developed delayed anti-HBs positivity without anti-HBc seroconversion, HBsAg positivity, or detectable HBV-DNA, suggesting possible subclinical HBV antigen exposure from the allograft. Conclusions: Kidney transplantation from donors with resolved HBV infection was not associated with clinically evident HBV infection, although transient serological changes were observed. Optimized vaccination strategies and structured post-transplant monitoring may enhance the safety of transplantations involving such donors. Full article

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

Oxidative stress and inflammation are key drivers of kidney injury and disease progression. In this context, the role of sialic acids emerged as a critical regulatory layer linking redox imbalance, immune activation, and tissue damage. Sialic acids are terminal negatively charged residues that regulate complement activity, immune cell signaling, and the structural integrity of the glomerular filtration barrier. Alterations in sialylation, resulting from impaired biosynthesis or increased sialidase activity, disrupt immune homeostasis, enhance inflammatory responses, and promote complement-mediated injury. In the kidney, these mechanisms contribute to podocyte dysfunction, glomerular inflammation, and fibrosis and are implicated in glomerulopathies, transplantation, and plasma cell dyscrasias. Emerging evidence also highlights the therapeutic potential of targeting sialic acid metabolism through inhibition of desialylation or restoration of sialylation pathways. Overall, sialic acids represent dynamic modulators at the intersection of oxidative stress and immunity, offering novel opportunities for biomarker development and mechanism-based therapies in kidney disease. Full article

Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis. This prospective single-center, non-randomized, single-arm cohort study enrolled renal transplant recipients with refractory anemia, defined as hemoglobin (Hb) ≤10 g/dL despite receiving the maximum doses of erythropoiesis-stimulating agents for 12 weeks. The studied parameters were Hb, ferritin, iron saturation index, glomerular filtration rate (eGFR), and C-reactive protein (CRP). Follow-up assessments were conducted at 4, 8, and 12 weeks after starting Roxadustat. The primary endpoint was the proportion of patients achieving Hb > 11 g/dL at 12 weeks. Secondary endpoints included changes from baseline in studied parameters and adverse effects. Twenty recipients (11 male, 9 female) with a median age of 69.0 years and a median time post-transplant of 62.5 months were included. Median baseline eGFR was 16.5 mL/min/1.73 m². At 12 weeks, 19 of 20 (95%) achieved Hb > 11 g/dL. Median Hb increased significantly from 9.1 g/dL to 11.5 g/dL, with a median individual change of +2.7 g/dL (IQR 1.7–3.4; p < 0.001). The only non-responder increased Hb from 9.5 to 10.2 g/dL. Ferritin decreased significantly over 12 weeks, whereas no statistically significant changes were observed in transferrin saturation, CRP, or eGFR. No serious adverse events were observed. In this prospective cohort, roxadustat was associated with short-term hemoglobin improvement and high Hb target attainment; however, these findings should be interpreted cautiously given the single-arm design and limited sample size. Full article

Background: Pulmonary fibrosis (PF) is a chronic, progressive lung disease with limited treatment options. Liuweidihuang pill (LDP), a classical formula for kidney-yin deficiency, has been reported to have anti-inflammatory and anti-oxidative activities, suggesting potential relevance to PF. Purpose: This study evaluated whether LDP attenuates bleomycin-induced PF in mice and whether gut microbiota remodeling may contribute to its protective effects. Methods: Mice received intratracheal bleomycin followed by LDP gavage. Lung pathology was assessed by hematoxylin–eosin (HE) and Masson staining. Inflammatory cytokines, hydroxyproline (HYP), and α-SMA were measured. LDP and LDP-containing serum were profiled by UPLC-MS. The gut microbiota was analyzed using 16S rDNA sequencing. To further explore whether microbiota-related changes were associated with the protective phenotype, fecal microbiota transplantation (FMT) and probiotic VSL#3 intervention were performed. In addition, LDP-containing serum was tested in a TGF-β1-induced EMT model in A549 cells. Results: LDP reduced lung index, inflammatory infiltration, interstitial fibrosis, α-SMA expression, HYP content, and pro-inflammatory cytokine levels in bleomycin-treated mice. These effects were accompanied by gut microbiota remodeling and transcriptomic changes related to inflammation, metabolism, and fibrosis. VSL#3 partially reproduced the protective phenotype, whereas FMT showed limited efficacy. LDP-containing serum had a limited inhibitory effect on EMT inhibited EMT in vitro, suggesting that systemic host responses may contribute to the in vivo effect. Conclusions: LDP attenuated early bleomycin-induced PF and was associated with reduced inflammation and gut microbiota remodeling. These findings suggest a possible role for microbiota–host interactions in LDP-associated protection; however, causal directionality, key active effectors, and protein-level pathway validation remain unresolved. Full article

Purpose: Simultaneous liver–kidney transplantation (SLK) eligible candidates may receive SLK or liver-alone transplant (LA) with access to kidney transplant after initial LA (KAL). We aimed to characterize SLK-eligible recipient outcomes according to treatment approach. Methods: This study utilized 2017–2023 SRTR data to identify SLK-eligible deceased donor liver transplants. Recipients were placed into two groups based on whether SLK was performed; non-SLK patients were sub-stratified into LA and KAL cohorts. After baseline comparisons, 2-year patient and graft survival outcomes were characterized by univariable and multivariable Cox proportional hazard regression and Kaplan–Meier analysis. Results: Among 4879 candidates identified, 3746 (76.8%) underwent SLK, 1023 (21.0%) LA, and 110 (2.3%) KAL. SLK recipients maintained the highest eGFRs at 6 months, 1 year, and 2 years post-transplant (p < 0.01). Compared to SLK recipients, non-SLK recipients had a higher 2-year risk of mortality (aHR 2.46, p < 0.01), all-cause events (aHR 1.91, p < 0.01), and liver graft failure (HR 1.55, p = 0.02). LA conferred a higher 2-year mortality risk (aHR 2.98, p < 0.01) and all-cause event risk (aHR 2.25, p < 0.01), while KAL had comparable mortality risk to SLK (aHR 0.43, p = 0.40). Conclusions: When SLK-eligible candidates undergo transplants, SLK remains the optimal path forward, even when a safety net kidney can be performed. Full article

The endothelial glycocalyx (EG) is a dynamic endothelial surface layer composed of proteoglycans, glycosaminoglycans, glycoproteins, and adsorbed plasma proteins that regulates permeability, mechanotransduction, leukocyte trafficking, coagulation, and nitric oxide signaling. In kidney transplantation (KT), the EG is exposed to cumulative injury from recipient uremia, donor instability, preservation, machine perfusion, reperfusion, rejection, and immunosuppressive toxicity. This narrative review summarizes EG biology in KT, with emphasis on biomolecular findings relevant to ischemia–reperfusion injury, delayed graft function, rejection, and chronic allograft injury. Particular attention is given to syndecan-1, heparan sulfate, heparanase, soluble thrombomodulin, matrix metalloproteinases, angiopoietin-2/Tie2 signaling, selectins, miR-126, extracellular vesicles, and urinary or perfusate-derived readouts. Current evidence is biologically coherent but uneven: human data are largely observational, whereas many therapeutic concepts remain preclinical or exploratory. Glycocalyx-centered phenotyping may eventually improve risk stratification and trial enrichment, but clinical implementation will require standardized sampling, sample-source-aware biomarker panels, prospective validation, and clear separation between mechanistic plausibility and proven clinical utility. Full article

Background: Ischemia-reperfusion injury (IRI) impairs kidney transplants. Diazepam can reduce IRI through peripheral benzodiazepine receptors. We aimed to evaluate the effect of diazepam premedication on the IRI of the rat kidney. Methods: Fourteen days after unilateral nephrectomy, male Sprague-Dawley rats underwent a 45 min sole kidney ischemia. Sixty minutes prior to ischemia, the animals were randomly assigned to a subcutaneous injection of 0.75 mg diazepam (n = 28) or 0.5 mL 0.9% NaCl (n = 31). Results: After 48 h, serum creatinine of diazepam-administered rats was lower and creatinine clearance was higher than in controls (119.8 ± 73.3 vs. 217.5 ± 105.3 µmol/L, p < 0.01 and 0.14 ± 0.07 vs. 0.08 ± 0.05 mL/min/100 g BM, p < 0.01, respectively). Moreover, the former had lower urinary losses of sodium and potassium (fractional excretions of 1.24 ± 1.39% vs. 2.87 ± 3.66%, p = 0.02 and 111.1 ± 95.7% vs. 199.0 ± 143.3%, p < 0.01, respectively). After 7 days, diazepam-treated rats remained superior vs. controls, regarding serum creatinine (53.7 ± 12.7 vs. 77.6 ± 21.3 µmol/L, p < 0.01), creatinine clearance (0.22 ± 0.08 vs. 0.17 ± 0.06 mL/min/100 g BM, p < 0.01), potassium sparing (50.2 ± 31.7% vs. 73.4 ± 38.7% excretion, p < 0.01), and renal edema (1.92 ± 0.45 vs. 2.30 ± 0.61 g of kidney mass, p < 0.01). Furthermore, their 24 h proteinuria was marginally reduced (4.03 ± 2.62 vs. 5.06 ± 2.74 mg, p = 0.06). Conclusions: Administration of diazepam preceding renal ischemia attenuates subsequent kidney injury in rats. Benzodiazepines may be beneficial prior to kidney transplantation. Full article

Background/Objectives: Early transient endocrine dysfunction after simultaneous pancreas-kidney transplantation (SPK) frequently triggers urgent investigations to exclude thrombosis, pancreatitis, or rejection, yet many recipients recover during the index admission. We tested whether pre-transplant day zero (D0) serum Fourier-transform infrared spectroscopy (FTIRS) captures a biochemical fingerprint associated with a Start&Stop trajectory (initial insulin independence followed by transient dysfunction with recovery). Methods: In a single-center retrospective case-control study nested within 104 consecutive SPK recipients with available D0 serum, 12 Start&Stop cases were matched 1:1 to 12 No-Stop controls. Serum FTIR spectra went through structured quality control and standardized preprocessing. A Naïve Bayes classifier with Fast Correlation-Based Filter (FCBF) feature selection was evaluated using leave-one-out cross-validation (LOOCV) and label-permutation analysis. Results: Under LOOCV, the primary FTIRS model (Savitzky-Golay second derivative; 600–900 and 2800–3400 cm⁻¹) achieved excellent discrimination (ROC-AUC 1.00) with accuracy 0.958 and F1 score 0.958. Discrimination collapsed under label permutation (ROC-AUC 0.461), supporting a non-random label-spectrum association. Discriminant information mapped mainly to carbohydrate/glycoprotein-associated bands (~946–1161 cm⁻¹), protein structural contributions near the amide III region (~1300 cm⁻¹), and lipid/protein stretching modes (~2865–3163 cm⁻¹), consistent with a multicomponent systemic biochemical state. Conclusions: In this exploratory matched case-control cohort, pre-transplant D0 serum FTIRS signatures were associated with the subsequent Start&Stop phenotype after SPK. These findings should be interpreted as recipient-side exploratory risk-stratification signals rather than clinically actionable decision tools. Larger multicenter validation in unselected cohorts, with standardized endpoint adjudication, preanalytical control, fully nested model development and inter-instrument harmonization, is required before clinical implementation or population-level risk calibration. Full article

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

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

Background: Post-transplant immune heterogeneity may influence kidney allograft outcomes, yet the clinical relevance of circulating T-cell phenotypes remains incompletely defined. We aimed to identify 12-month post-transplant data-driven T-cell clusters and examine their relation to graft-function patterns during the first post-transplant year. Methods: Peripheral blood T-cell subpopulations were analyzed in 112 kidney transplant recipients at 12 months post-transplantation using flow cytometry. Standardized subpopulation frequencies underwent unsupervised hierarchical clustering, with principal component analysis used for visualization. Longitudinal graft function trajectories (eGFR and serum creatinine at 1, 3, 6, and 12 months) were analyzed using generalized estimating equation models, including time-by-cluster interactions. Results: Three recipient clusters were identified: a CD8-skewed cytotoxic/senescent cluster, an innate-like cytotoxic cluster, and a CD4-dominant cluster. Cluster robustness was supported by complementary k-means analysis. Older recipient age and baseline cytomegalovirus seropositivity were associated with the CD8-skewed cluster. Recipients assigned to different T12 clusters showed differences in serum creatinine levels and graft function trajectories, although some associations were attenuated after additional adjustment for transplant-related factors. Conclusions: In this cohort, unsupervised clustering identified distinct post-transplant T-cell profiles associated with early graft function patterns. These findings are hypothesis-generating and require longitudinal and external validation. Full article

Background/Objectives: Accurate kidney segmentation from magnetic resonance imaging (MRI) in kidney-transplant patients is essential for quantitative graft assessment, yet it remains challenging due to low tissue contrast, intensity inhomogeneity, and inter-patient anatomical variability introduced by surgical graft placement. Methods: We propose a 3D adversarial segmentation framework that incorporates probabilistic appearance and anatomical shape priors into a residual conditional generative adversarial network (GAN). The framework integrates image-driven and prior-guided information to improve boundary delineation under challenging imaging conditions and is evaluated on 100 kidney-transplant patients across T2-weighted imaging, BOLD-MRI, and DW-MRI using leave-one-out cross-validation. Results: The proposed method achieves mean Dice scores of 90.86% on T2-weighted imaging, 92.02% on BOLD-MRI, and 94.00% on DW-MRI. Consistent performance across all modalities demonstrates robustness under heterogeneous MRI acquisitions. The incorporation of prior guidance improves segmentation stability and anatomical consistency, particularly in low-contrast modalities. Conclusions: The proposed framework enables reliable kidney delineation across multiple MRI sequences, supporting consistent extraction of quantitative imaging biomarkers. This capability facilitates noninvasive assessment of renal graft function and supports longitudinal monitoring of transplant patients. Full article