Browsing by Author "Reich, Heather N."

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    CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update
    (The Journal of Rheumatology Publishing Co. Ltd., 2022-04) Mendel, Arielle; Ennis, Daniel; Go, Ellen; Bakowsky, Volodko; Baldwin, Corisande; Benseler, Susanne M.; Cabral, David A.; Carette, Simon; Clements-Baker, Marie; Clifford, Alison H.; Cohen Tervaert, Jan Willem; Cox, Gerard; Dehghan, Natasha; Dipchand, Christine; Dhindsa, Navjot; Famorca, Leilani; Fifi-Mah, Aurore; Garner, Stephanie; Girard, Louis-Philippe; Lessard, Clode; Liang, Patrick; Noone, Damien; Makhzoum, Jean-Paul; Milman, Nataliya; Pineau, Christian A.; Reich, Heather N.; Rhéaume, Maxime; Robinson, David B.; Rumsey, Dax G.; Towheed, Tanveer E.; Trudeau, Judith; Twilt, Marinka; Yacyshyn, Elaine; Yeung, Rae S. M.; Barra, Lillian B.; Khalidi, Nader; Pagnoux, Christian; Pediatrics, School of Medicine
    Objective In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aimed to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. Methods A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014-September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a two-step modified Delphi procedure to reach >80% consensus on the inclusion, wording and grading of each new and revised recommendation. Results Eleven new and 16 revised recommendations were created, and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary appendix for practical use was revised to reflect the updated recommendations. Conclusion The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.
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    Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study
    (Elsevier, 2018-08-03) Selewski, David T.; Ambruzs, Josephine M.; Appel, Gerald B.; Bomback, Andrew S.; Matar, Raed Bou; Cai, Yi; Cattran, Daniel C.; Chishti, Aftab S.; D’Agati, Vivette D.; D’Alessandri-Silva, Cynthia J.; Gbadegesin, Rasheed A.; Hogan, Jonathan J.; Iragorri, Sandra; Jennette, J. Charles; Julian, Bruce A.; Khalid, Myda; Lafayette, Richard A.; Liapis, Helen; Lugani, Francesca; Mansfield, Sarah A.; Mason, Sherene; Nachman, Patrick H.; Nast, Cynthia C.; Nester, Carla M.; Noone, Damien G.; Novak, Jan; O’Shaughnessy, Michelle M.; Reich, Heather N.; Rheault, Michelle N.; Rizk, Dana V.; Saha, Manish K.; Sanghani, Neil S.; Sperati, C. John; Sreedharan, Rajasree; Srivastava, Tarak; Swiatecka-Urban, Agnieszka; Twombley, Katherine; Vasylyeva, Tetyana L.; Weaver, Donald J.; Yin, Hong; Zee, Jarcy; Falk, Ronald J.; Gharavi, Ali G.; Gillespie, Brenda W.; Gipson, Debbie S.; Greenbaum, Larry A.; Holzman, Lawrence B.; Kretzler, Matthias; Robinson, Bruce M.; Smoyer, William E.; Flessner, Michael; Guay-Woodford, Lisa M.; Kiryluk, Krzysztof; CureGN Consortium; Pediatrics, School of Medicine
    Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.
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    Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial
    (American Medical Association, 2022) Lv, Jicheng; Wong, Muh Geot; Hladunewich, Michelle A.; Jha, Vivekanand; Hooi, Lai Seong; Monaghan, Helen; Zhao, Minghui; Barbour, Sean; Jardine, Meg J.; Reich, Heather N.; Cattran, Daniel; Glassock, Richard; Levin, Adeera; Wheeler, David C.; Woodward, Mark; Billot, Laurent; Stepien, Sandrine; Rogers, Kris; Chan, Tak Mao; Liu, Zhi-Hong; Johnson, David W.; Cass, Alan; Feehally, John; Floege, Jürgen; Remuzzi, Giuseppe; Wu, Yangfeng; Agarwal, Rajiv; Zhang, Hong; Perkovic, Vlado; TESTING Study Group; Medicine, School of Medicine
    Importance: The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. Objective: To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. Design, setting, and participants: An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. Interventions: Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). Main outcomes and measures: The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. Results: Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]). Conclusions and relevance: Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy.
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    The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics
    (Karger, 2021) Wong, Muh Geot; Lv, Jicheng; Hladunewich, Michelle A.; Jha, Vivekanand; Hooi, Lai Seong; Monaghan, Helen; Zhao, Minghui; Barbour, Sean; Reich, Heather N.; Cattran, Daniel; Glassock, Richard; Levin, Adeera; Jardine, Meg J.; Wheeler, David C.; Woodward, Mark; Billot, Laurent; Chan, Tak Mao; Liu, Zhi-Hong; Johnson, David W.; Cass, Alan; Feehally, John; Floege, Jürgen; Remuzzi, Giuseppe; Wu, Yangfeng; Agarwal, Rajiv; Zhang, Hong; Perkovic, Vlado; Medicine, School of Medicine
    Introduction: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. Methods: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment. Results: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. Conclusions: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN.