Publications by authors named "Sean Barbour"

Article Synopsis
  • * This research analyzed data from 1912 patients over an average of 6.8 years, discovering that corticosteroids did not significantly increase cardiovascular risk, but higher doses of calcineurin inhibitors and certain antimetabolites were linked to greater risks.
  • * The study highlights that different immunosuppressive treatments carry varying cardiovascular risks, which should be a crucial factor in choosing therapy for patients with glomerular disease.
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Background: B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in the pathogenesis of IgA nephropathy. Atacicept is a novel fully humanized fusion protein, self-administered at home by subcutaneous injection, that binds and inhibits BAFF and APRIL. By inhibiting BAFF and APRIL, atacicept targets the underlying B-cell–mediated pathogenesis driving disease progression.

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Article Synopsis
  • * In a study involving 947 children with IgAN, the revised tool outperformed the original in terms of model fit and predictive accuracy for 4-year outcomes, showing enhanced calibration and statistical values.
  • * The findings indicated that kidney function (eGFR) trajectories were non-linear, with higher-risk children showing a faster decline, suggesting that the updated prediction should be used for ongoing risk assessment after one or two years following biopsy.
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Introduction: The therapeutic effects of steroids in immunoglobulin A nephropathy (IgAN) global (TESTING) study reported that methylprednisolone reduces the risk of major kidney events in individuals with IgAN at high risk of disease progression compared to supportive care alone but is associated with increased serious adverse events (SAEs) primarily with full-dose therapy. The risk benefit balance of the reduced-dose methylprednisolone regimen is examined in this prespecified analysis of the reduced-dose cohort of the TESTING trial.

Methods: Between 2017 and 2019, patients with IgAN, proteinuria ≥1 g/d despite 3 months of renin-angiotensin-system blockade and estimated glomerular filtration rate (eGFR) 30 to 120 ml/min per 1.

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Background And Hypothesis: The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health-care payers.

Methods: A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health-care payer with a lifetime time horizon.

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Atacicept is a first-in-class, dual anti-B-cell Activation Factor-A Proliferation-Inducing Ligand fusion protein in clinical evaluation for treatment of IgA nephropathy. To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b clinical trial ORIGIN enrolled 116 individuals with biopsy-proven IgA nephropathy. Participants were randomized to atacicept 150, 75, or 25 mg versus placebo once weekly for up to 36 weeks.

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Article Synopsis
  • Immunoglobulin A nephropathy (IgAN) is a major cause of kidney failure and, until recently, had limited treatment options.
  • New clinical trials, such as the TESTING trial, show promise in using glucocorticoids and other therapies to slow kidney disease progression and improve safety.
  • The challenge now lies in selecting the most effective treatment for individual patients, as various new therapies are becoming available for this condition.
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Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.

Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists.

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Article Synopsis
  • IgA nephropathy is a common kidney disease characterized by proteinuria, which signals a risk of kidney failure, and complement activation contributes to its progression.
  • Cemdisiran, an experimental treatment that inhibits the production of a specific complement protein (C5), was evaluated in a study involving adults with IgA nephropathy to see if it could reduce proteinuria.
  • The results showed that cemdisiran significantly reduced protein levels in urine and blood levels of C5, with mostly mild side effects, suggesting it may be a promising therapy for managing IgA nephropathy.
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Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases and the development of malignancies, with an estimated risk ranging from 5 to 11%. These malignancies include solid organ tumours as well as haematologic malignancies such as lymphoma and leukaemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of glomerular disease cases that were potentially secondary to an underlying malignancy, misclassification of glomerular disease type and ascertainment bias arising from an increased likelihood of physician encounters compared with the general population.

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Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

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Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

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Purpose Of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health's Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely.

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Rationale & Objective: Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease.

Study Design: Observational cohort study.

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Purpose Of Review: The use of corticosteroids to treat IgA nephropathy (IgAN) has been limited by many controversies related to uncertain benefit and safety concerns. Recent trials have tried to address these limitations.

Recent Findings: After being paused because of an excess of adverse events in the full-dose steroid arm, the TESTING trial compared a reduced dose of methylprednisolone to placebo in patients with IgAN after optimization of supportive therapy.

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Background: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination.

Methods: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available).

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Background And Objectives: C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years.

Design, Setting, Participants, & Measurements: To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients.

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Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene () gene and is characterized by lipoprotein thrombi in glomerular capillaries. Here, we describe a case of LPG, the first to be reported from Canada and the first case of LPG in North America to be associated with the Tokyo/Maebashi mutation (p.Leu162_Lys164del, traditional nomenclature 142_144del).

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Rationale & Objective: Little is known about the risk of cardiovascular disease (CVD) in patients with various primary glomerular diseases. In a population-level cohort of adults with primary glomerular disease, we sought to describe the risk of CVD compared with the general population and the impact of traditional and kidney-related risk factors on CVD risk.

Study Design: Observational cohort study.

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Article Synopsis
  • The study aimed to determine the effectiveness of methylprednisolone, a glucocorticoid, in preventing kidney function decline in patients with IgA nephropathy who are at high risk for such decline.
  • Conducted as a double-blind, randomized clinical trial with 503 participants across multiple countries, the results indicated that those receiving methylprednisolone had a significantly lower rate of serious kidney outcomes compared to those on placebo.
  • After 4.2 years of follow-up, the primary composite outcome occurred in 28.8% of the methylprednisolone group versus 43.1% of the placebo group, showcasing methylprednisolone's potential benefits for patients with this kidney condition.
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The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults.

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Aims: To assess the effect of sodium-glucose cotransporter-2 inhibitor dapagliflozin on natriuresis, blood pressure (BP) and volume status in patients with chronic kidney disease (CKD) without diabetes.

Materials And Methods: We performed a mechanistic open-label study (DAPASALT) to evaluate the effects of dapagliflozin on 24-hour sodium excretion, 24-hour BP, extracellular volume, and markers of volume status during a standardized sodium diet (150 mmol/d) in six patients with CKD. In parallel, in a placebo-controlled double-blind crossover trial (DIAMOND), we determined the effects of 6 weeks of dapagliflozin on markers of volume status in 53 patients with CKD.

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