For a study, researchers sought to determine the effectiveness and side effects of methylprednisolone in individuals with IgA nephropathy who were at high risk of kidney function deterioration. 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 eGFR of 20 to 120 mL/min/1.73 m^2 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. Participants were randomly assigned to either oral methylprednisolone (0.6-0.8 mg/kg/d at the start, up to 48 mg/d at the end, tapering by 8 mg/d/mo; n = 136) or placebo (n = 126). An excess of serious infections was identified after 262 participants were randomized, resulting in dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and the addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). The primary end outcome was a 40% decrease in eGFR, renal failure (dialysis, transplant), or death from kidney disease. There were 11 secondary outcomes, one of which was renal failure.
The study was completed by 493 (98%) of the 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m^2; mean proteinuria, 2.46 g/d). The primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group versus 106 (43.1%) in the placebo group over a mean of 4.2 years of follow-up (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 impact on the primary outcome was found across all doses when compared to the relevant persons 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, 0.41-0.81). (95% CI, 0.11-0.65). 9 of the 11 prespecified secondary end points showed statistically 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%]). Significant adverse events were more common with methylprednisolone than with placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), especially with full-dose medication over its corresponding placebo (22 [16.2%] vs 4 [3.2%]). Treatment with oral methylprednisolone for 6 to 9 months, compared to placebo, significantly decreased the risk of the composite endpoint of renal function decline, kidney failure, or death owing to kidney disease in patients with IgA nephropathy at high risk of progression.