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Steroid Pretreatment of Organ Donors to Prevent Postischemic Renal Allograft Failure: A Randomized, Controlled Trial

ABSTRACT: Comparison between pretreated donor grafts corticosteroid vs. placebo

ORGANISM(S): Homo sapiens

PROVIDER: GSE14700 | GEO | 2010/08/17

SECONDARY ACCESSION(S): PRJNA112335

REPOSITORIES: GEO

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Steroid Pretreatment of Organ Donors to Prevent Postischemic Renal Allograft Failure: A Randomized, Controlled Trial

Project description:Comparison between pretreated donor grafts corticosteroid vs. placebo Prospective, randomised, double-blind, placebo-control trial, xls files contain normalized data (Default Total Intensity Normalization, see Stanford Microarray Database website), gpr files the raw data

2010-08-17 | E-GEOD-14700 | biostudies-arrayexpress

Steroid pretreatment of organ donors does not impact on early rejection and long-term kidney allograft survival: Results from a multicenter randomized, controlled trial.

Project description:Steroid pretreatment of deceased donors reduces inflammation in allografts and is recommended by organ procurement guidelines. The impact on long-term graft outcome, however, remains elusive. In this multicenter randomized controlled trial, 306 deceased donors providing organs for 455 renal transplant recipients were randomized to 1000 mg of methylprednisolone or placebo prior to organ procurement (ISRCTN78828338). The incidence of biopsy-confirmed rejection (Banff>1) at 3 months was 23 (10%) in the steroid group and 26 (12%) in the placebo group (P = .468). Five-year functional graft survival was 84% and 82% for the steroid group and placebo group, respectively (P-value = .941). The hazard ratio of functional graft loss was 0.90 (95% confidence interval 0.57-1.42, P = .638) for steroid vs placebo in a multivariate Cox model. We did not observe effect modification by any of the predictors of graft survival and treatment modality. A robust sandwich estimate was used to account for paired grafts of some donors. The mean estimated GFR at 5 years was 47 mL/min per 1.73 m2 in the steroid group and 48 mL/min per 1.73 m2 in the placebo group (P = .756). We conclude that steroid pretreatment does not impact on long-term graft survival. In a donor population with higher risk of delayed graft function, however, repetitive and higher doses of steroid treatment may result in different findings.

| S-EPMC6563104 | biostudies-literature

Subclinical inflammation and chronic renal allograft injury in a randomized trial on steroid avoidance in pediatric kidney transplantation.

Project description:Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.

| S-EPMC3459071 | biostudies-literature

Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial.

Project description:BACKGROUND:Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF. METHODS:The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg-1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n =?648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group). DISCUSSION:Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016.

| S-EPMC5905107 | biostudies-literature

Circulating mitochondria in organ donors promote allograft rejection.

Project description:The innate immune system is a critical regulator of the adaptive immune responses that lead to allograft rejection. It is increasingly recognized that endogenous molecules released from tissue injury and cell death are potent activators of innate immunity. Mitochondria, ancestrally related to bacteria, possess an array of endogenous innate immune-activating molecules. We have recently demonstrated that extracellular mitochondria are abundant in the circulation of deceased organ donors and that their presence correlates with early allograft dysfunction. Here we demonstrate the ability of mitochondria to activate endothelial cells (ECs), the initial barrier between a solid organ allograft and its host. We find that mitochondria exposure leads to the upregulation of EC adhesion molecules and their production of inflammatory cytokines and chemokines. Additionally, mitochondrial exposure causes dendritic cells to upregulate costimulatory molecules. Infusion of isolated mitochondria into heart donors leads to significant increase in allograft rejection in a murine heterotopic heart transplantation model. Finally, co-incubation of human peripheral blood mononuclear cells with mitochondria-treated ECs results in increased numbers of effector (IFN-γ+ , TNF-α+ ) CD8+ T cells. These data indicate that circulating extracellular mitochondria in deceased organ donors may directly activate allograft ECs and promote graft rejection in transplant recipients.

| S-EPMC6591073 | biostudies-literature

A phase 2 Randomized Controlled Trial of Adjuvant Tumor-Infiltrating Lymphocytes for Pretreatment Epstein-Barr Virus DNA-selected High-Risk Nasopharyngeal Carcinoma Patients

Project description:420 locoregionally advanced NPC patients underwent pEBV DNA screening. 156 patients (37.1%) who had pEBV DNA ≥4000 copies/mL were included and randomly assigned to CCRT plus TIL infusion group (n=78) and CCRT alone group (n=78). Outcomes were classified as patients with a poor outcome (nonresponders) and patients with a favorable outcome (responders). Single cell RNA sequencing (scRNA-seq) for infused TIL products in responder and non-responder.

2024-06-30 | GSE179224 | GEO

Transcriptomic profile of murine abdominal aorta allograft undergoing chronic rejection

Project description:Graft vascular disease (GVD) is a major problem limiting the long-term survival of grafts. To determine the underlying mechanisms of GVD during chronic phase, we performed murine abdominal aorta transplantation. Donor aortas from C57Bl/6 (H-2b) mice were transplanted into C57Bl/6 (H-2b) mice, and we call this group isograft (ISO). Donor aortas from BALB/c (H-2d) mice were transplanted into C57Bl/6 (H-2b) mice, and we call this group allograft (ALLO). In brief, donor abdominal aortas were isolated and the branch vessels were ligated, while the recipient vessels were cut from the midsection using microscopic scissors. The recipient and donor vessels were anastomosed with a cuff suture. 4 weeks after aorta transplantation, the mice were sacrificed for transcriptomic sequencing and analyzing of the aortic grafts.

2022-11-19 | GSE161898 | GEO

CT with hepatic arterioportography as a pretreatment examination for hepatocellular carcinoma patients: a randomized controlled trial.

Project description:OBJECTIVES: The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT. METHODS: In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence. RESULTS: A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73-1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77-1.71). CONCLUSIONS: CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.

| S-EPMC3734528 | biostudies-other

Cold plasma pretreatment reinforces the lignocellulose-derived aldehyde inhibitors tolerance and bioethanol fermentability for Zymomonas mobilis

Project description:To investigate the molecular mechanism of the increased bioethanol fermentability, we carried out RNA-Seq sequencing assays for the wild and mutant strain Z. mobilis after pretreated with cold plasma. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells at one time points.

2023-04-15 | GSE228538 | GEO

Lung function, airway and peripheral basophils and eosinophils are associated with molecular pharmacogenomic endotypes of steroid response in severe asthma.

Project description:Sputum airway cells transcriptome from 19 asthmatics from the Severe Asthma Research Program at baseline and 6-8 weeks follow-up after a 40mg dose of intramuscular corticosteroid triamcinolone acetonide.

2022-06-09 | GSE184433 | GEO

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