Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial

Lv J 1 , Wong MG 2 , Hladunewich MA 3 , Jha V 4 , Hooi LS 5 , Monaghan H 2 Show all authors , Zhao M 1 , Barbour S 6 , Jardine MJ 7 , Reich HN 8 , Cattran D 8 , Glassock R 9 , Levin A 6 , Wheeler DC 10 , Woodward M 11 , Billot L 2 , Stepien S 2 , Rogers K 2 , Chan TM 12 , Liu ZH 13 , Johnson DW 14 , Cass A 2 , Feehally J 15 , Floege J 16 , Remuzzi G 17 , Wu Y 18 , Agarwal R 19 , Zhang H 1 , Perkovic V 2 , TESTING Study Group

Affiliations 

  • 1 Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
  • 2 The George Institute for Global Health, University of New South Wales, Sydney, Australia
  • 3 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
  • 4 The George Institute for Global Health India, UNSW, New Delhi, India
  • 5 Sultanah Aminah Hospital, Johor Bahru, Malaysia
  • 6 The University of British Columbia, Vancouver, British Columbia, Canada
  • 7 NHMRC Clinical Trials Centre, University of Sydney, Australia
  • 8 University Health Network, Toronto, Ontario, Canada
  • 9 David Geffen School of Medicine, University of California, Los Angeles
  • 10 Department of Renal Medicine, University College London, United Kingdom
  • 11 The George Institute for Global Health, School of Public Health, Imperial College London, United Kingdom
  • 12 Department of Medicine, The University of Hong Kong, Hong Kong, SAR of China
  • 13 Research Institute of Nephrology, Jinling Hospital, Nanjing, China
  • 14 Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia
  • 15 University of Leicester, Leicester, United Kingdom
  • 16 Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany
  • 17 Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
  • 18 Peking University Clinical Research Institute, Beijing, China
  • 19 Indiana University School of Medicine, Indianapolis
JAMA, 2022 May 17;327(19):1888-1898.
PMID: 35579642 DOI: 10.1001/jama.2022.5368

Abstract

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 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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