Publications by authors named "Rheault M"
Article Synopsis
- IgA vasculitis (IgAV) is a pediatric disease characterized by skin and systemic symptoms, and researchers conducted comprehensive studies involving genome, transcriptome, and proteome analyses on a large cohort of IgAV patients and controls to better understand the disease mechanisms.* -
- Significant associations were found with specific genetic risk factors, including two novel non-HLA loci linked to IgA receptor functioning, which may contribute to disease development through altered immune responses.* -
- Systems biology approaches helped identify key regulatory networks and master regulators in myeloid cells, along with 21 genetic loci that overlap with IgA nephropathy, suggesting shared pathways in these related conditions.*
BACKGROUNDIt is unknown whether the risk of kidney disease progression and failure differs between patients with and without genetic kidney disorders.METHODSThree cohorts were evaluated: the prospective Cure Glomerulonephropathy Network (CureGN) and 2 retrospective cohorts from Columbia University, including 5,727 adults and children with kidney disease from any etiology who underwent whole-genome or exome sequencing. The effects of monogenic kidney disorders and APOL1 kidney-risk genotypes on the risk of kidney failure, estimated glomerular filtration rate (eGFR) decline, and disease remission rates were evaluated along with diagnostic yields and the impact of American College of Medical Genetics secondary findings (ACMG SFs).
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- Alport syndrome (AS) is a genetic disorder that leads to kidney failure, hearing loss, and eye issues due to faulty collagen production caused by mutations in COL4A3-5 genes.
- It encompasses a range of genetic inheritance patterns and is recognized as the "Alport spectrum disorder," making it the most common genetic cause of kidney disease.
- The severity and progression of AS can differ greatly based on factors like gender, inheritance type, and specific mutations, and the article will cover its epidemiology, diagnosis, prognosis, and treatment options.
Article Synopsis
- Sparsentan, a new dual endothelin angiotensin receptor antagonist, was evaluated in the ongoing phase 2 DUET trial for treating focal segmental glomerulosclerosis (FSGS) and showed a significant reduction in proteinuria over an 8-week period compared to irbesartan.
- The study involved 109 patients with FSGS and tracked their response to various doses of sparsentan (200, 400, and 800 mg/d) for up to 4.6 years, measuring urinary protein levels, glomerular filtration rate, and blood pressure at regular intervals.
- Results indicated that 52.8% of patients achieved partial remission within 9 months, which was linked to a
Article Synopsis
- The phase 3 DUPLEX trial is testing sparsentan, a new medication for patients with focal segmental glomerulosclerosis (FSGS), focusing on its safety and effectiveness.
- This global study involves 371 patients aged 8 to 75, comparing sparsentan 800 mg to irbesartan 300 mg, while analyzing their baseline characteristics related to FSGS severity.
- As the largest interventional study of its kind, DUPLEX aims to provide valuable insights into sparsentan's treatment effects across a diverse, worldwide patient population.
Background: Bloodstream infections (BSIs) are a leading cause of hospitalizations and mortality among patients receiving hemodialysis (HD) therapy, especially those with a central venous catheter (CVC) for dialysis access. The use of chlorhexidine impregnated catheter caps (ClearGuard) has been associated with a decrease in the rate of HD catheter-related BSIs (CA-BSIs) in adults; similar data have not been published for children.
Methods: We compared CA-BSI data from participating centers within the Standardizing Care to Improve Outcomes in Pediatric Endstage Kidney Disease (SCOPE) collaborative based on the center's use of ClearGuard caps for patients with HD catheter access.
Article Synopsis
- Primary membranous nephropathy (PMN) is rare in children, with limited existing data on its clinical course and histopathologic characteristics.
- In a study of 21 children with PMN from three U.S. centers, researchers identified novel antigens in biopsy specimens and correlated these findings with clinical outcomes.
- Results showed a good prognosis for most children, with about 60% testing positive for novel antigens like PLA2R and EXT1, which were linked to higher remission rates.
Article Synopsis
- The PROTECT trial, a phase 3 study, evaluated the effectiveness of sparsentan, a dual receptor antagonist, in reducing proteinuria compared to irbesartan in patients with immunoglobulin A nephropathy over 110 weeks.* -
- A total of 406 patients were randomly assigned to either sparsentan or irbesartan, with the primary goal being the change in proteinuria at 36 weeks and secondary goals related to kidney function and safety over the trial duration.* -
- The findings from the trial, which included a significant reduction in proteinuria with sparsentan, provide important insights into potential treatment strategies for patients with kidney conditions.*
Article Synopsis
- - A phase 3 trial investigated the long-term effects of sparsentan versus irbesartan in treating focal segmental glomerulosclerosis (FSGS) over 108 weeks, enrolling 371 patients aged 8 to 75.
- - At 36 weeks, sparsentan showed a significantly higher rate of partial remission of proteinuria (42%) compared to irbesartan (26%), and this positive response continued up to 108 weeks.
- - However, there were no significant differences in the estimated glomerular filtration rate (eGFR) slopes between the two groups at the final analysis, indicating that while proteinuria improved, kidney function as measured by eGFR remained similar with both treatments. *
Background: Early in the history of kidney transplantation, short-term graft survival was low. Yet some have had excellent long-term survival. Herein, we describe characteristics of pediatric recipients with > 40 years of graft survival currently alive with a functioning first graft.
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- * This study evaluates whether combining plasmapheresis with rituximab can effectively prevent the recurrence of FSGS in kidney transplant patients.
- * The combination therapy aims to offer a new treatment approach for recurrent FSGS, which currently has limited options and lacks standardized guidelines.
Rationale & Objective: Patients with glomerular disease (GN) may be at increased risk of severe COVID-19, yet concerns over vaccines causing disease relapse may lead to vaccine hesitancy. We examined the associations of COVID-19 with longitudinal kidney function and proteinuria and compared these with similar associations with COVID-19 vaccination.
Study Design: Observational cohort study from July 1, 2021, to January 1, 2023.
The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases represents the first update to this set of recommendations since the initial set of KDIGO guideline recommendations was published in 2012. The pace of growth in our molecular understanding of glomerular disease has quickened and a number of newer immunosuppressive and targeted therapies have been introduced since the original set of guideline recommendations, making such an update necessary. Despite these updates, many areas of controversy remain.
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- IgA nephropathy (IgAN) is a serious kidney disease linked to IgA buildup, and a large study identified 30 genetic risk factors associated with it.
- Fourteen new loci were discovered that suggest a connection between genetic influences and abnormal IgA levels.
- The research highlights inflammation-related pathways and potential drug targets, revealing that higher genetic risk scores are tied to earlier kidney failure.
Background: Inherited kidney diseases are a common cause of chronic kidney disease (CKD) in children. Identification of a monogenic cause of CKD is more common in children than in adults. This study evaluated the diagnostic yield and phenotypic spectrum of children who received genetic testing through the KIDNEYCODE sponsored genetic testing program.
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- Sparsentan is a new type of medication being tested in the ongoing PROTECT trial for adults with IgA nephropathy (IgAN), with potential benefits in reducing inflammation and improving blood flow, without suppressing the immune system.
- The PROTECT trial is a large, international study comparing the effectiveness and safety of sparsentan against the active drug irbesartan in patients with significant proteinuria who have not found success with previous treatments.
- Results from 404 enrolled patients showed a mix of demographics and health statuses, which will help understand how sparsentan works across different populations and stages of chronic kidney disease (CKD).
Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety.
Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries.
Efficient hepatitis C virus (HCV) RNA accumulation is dependent upon interactions with the human liver-specific microRNA, miR-122. MiR-122 has at least three roles in the HCV life cycle: it acts as an RNA chaperone, or 'riboswitch', allowing formation of the viral internal ribosomal entry site; it provides genome stability; and promotes viral translation. However, the relative contribution of each role in HCV RNA accumulation remains unclear.
View Article and Find Full Text PDFIntroduction: IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease.
Methods: Patients were categorized based on the intensity of light chain staining.
Background And Objectives: Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome.
Design, Setting, Participants, & Measurements: We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.