Background and objectives: Lower rates of living donor kidney transplant (LDKT) among transplant candidates who are black or older may stem from lower likelihoods of (1) recruiting potential living donors or (2) potential donors actually donating (donor "conversion").Design, setting, participants, & measurements: A single-center, retrospective cohort study was performed to determine race, age, and gender differences in LDKT, donor recruitment, and donor conversion.Results
The clinical significance of pre-transplant donorspecific antibodies (DSA), despite negative cytotoxicity and flow cytometry crossmatches (FCXMs), is unknown. We performed a retrospective cohort study of 60 living donor renal transplant recipients, all with pre-transplant cytotoxicity and T-cell and B-cell FCXMs that were negative. Twenty recipients had pre-transplant DSA detected by enzyme-linked immunosorbent assays (ELISA) and/or microbead methods. Forty contemporaneous DSA-negative controls were selected. In the DSA-positive group, after a median follow-up of 8.2 months (25-75% range, 5.4-22.8 months), patient survival was 100% and allograft survival was 95.0%. Acute humoral rejection (AHR) developed in four patients (20.0%). Three of the AHR episodes occurred within the first month posttransplant. Median serum creatinine at last follow-up was 1.3 mg/dL (25-75% range, 1.0-1.6 mg/dL), versus 1.1 mg/dL (25-75% range, 0.9-1.4 mg/dL) in the DSAnegative controls (p = 0.29). Only one of the 40 controls developed AHR (2.5%). Pre-transplant DSA was associated with a significantly increased incidence of AHR (p = 0.02 by log-rank test). In conclusion, despite negative pre-transplant cytotoxicity and FCXMs, renal transplant recipients with pre-transplant DSA detected by solid-phase methods may have an increased incidence of AHR and require close monitoring posttransplant.
Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with CO...
Three months of low-dose valganciclovir (450 mg/day) was as effective as ganciclovir (3 g/day) for prophylaxis of CMV disease after kidney and/or pancreas transplantation.
Funding information AlAnimal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation.We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19-subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu-treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant-related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu-treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180-days
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