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

JAMA. 2022 May 17;327(19):1888-1898. doi: 10.1001/jama.2022.5368.


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.

Trial registration: ClinicalTrials.gov Identifier: NCT01560052.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glomerulonephritis, IGA* / etiology
  • Glomerulonephritis, IGA* / therapy
  • Humans
  • Kidney
  • Male
  • Methylprednisolone* / administration & dosage
  • Methylprednisolone* / adverse effects
  • Proteinuria / etiology
  • Renal Dialysis
  • Renal Insufficiency* / chemically induced
  • Renal Insufficiency* / therapy


  • Methylprednisolone

Associated data

  • ClinicalTrials.gov/NCT01560052

Grants and funding