Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial

Jicheng Lv, Hong Zhang, Muh Geot Wong, Meg J. Jardine, Michelle Hladunewich, Vivek Jha, Helen Monaghan, Minghui Zhao, Sean Barbour, Heather Reich, Daniel Cattran, Richard Glassock, Adeera Levin, David Wheeler, Mark Woodward, Laurent Billot, Tak Mao Chan, Zhi Hong Liu, David W. Johnson, Alan CassJohn Feehally, Jürgen Floege, Giuseppe Remuzzi, Yangfeng Wu, Rajiv Agarwal, Hai Yan Wang, Vlado Perkovic, TESTING Study Group

    Research output: Contribution to journalArticle

    Abstract

    Importance: Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.

    Objective: To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.

    Design, Setting, and Participants: The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred.

    Interventions: Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.

    Main Outcomes and Measures: The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.

    Results: After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).

    Conclusions and Relevance: Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.

    Original languageEnglish
    Pages (from-to)432-442
    Number of pages11
    JournalJAMA: Journal of the American Medical Association
    Volume318
    Issue number5
    DOIs
    Publication statusPublished - 1 Aug 2017

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