IgA nephropathy remains poorly understood despite being the most common primary glomerular disease. Glucocorticoids are commonly used in clinical practice to manage IgA nephropathy, although the evidence in support of this is controversial, particularly with regard to the risk for immunosuppression in patients with advanced kidney disease. The present randomized controlled trial sought to determine the effect of oral methylprednisolone on renal function and related outcomes in patients with IgA nephropathy. The TESTING randomized controlled clinical trial consisted of 503 patients randomized, with 257 in the treatment group and 246 in the placebo group. Mean baseline characteristics of the enrolled group included an eGFR of 61.5mL/ min/1.73m2 and 24-hour urine protein of 2.46 g/day. “The TESTING trial… is the largest randomized clinical trial of therapy in IgA nephropathy yet conducted,” says co-author Richard Glassock, MD.

Seventy-four primary outcome events (7.3% per year) occurred in the treatment group and 106 (12.1% per year) occurred in the placebo group; this difference was significant in favor of the methylprednisolone group. The treatment group fared better in all kidney-related outcomes; however, there was an increased rate of
adverse events (ie, serious infections) in this group, and all-cause mortality was particularly higher prior to the methylprednisolone dose reduction. This randomized controlled trial concluded that high dose methylprednisolone administered over a 6-9- month period may be protective against progressive kidney fail ure in the setting of IgA nephropathy. However, high-dose glucocorticoids were associated with significant adverse effects and must be used with caution. “[The study] provides strong support for the routine use of oral, systemically acting glucocorticoids in patients with IgA nephropathy at high risk for progression of CKD despite supportive therapy with renin-angiotensin system inhibitors,” notes Dr. Glassock. “Moderate doses of steroids combined with chemoprophylaxis for Pneumocystis infections appear to be equally effective and safer than high doses of such steroid therapy. Steroid treatment for 6-9 months significantly slows but does not eliminate progressive CKD in highrisk IgA nephropathy.”

Strengths of this study include the large sample size and diverse study population, which make it more feasible to apply these results to the general population of patients with IgA nephropathy. “The results of the TESTING Trial will likely lead to more physicians (nephrologists) caring for patients with high-risk IgA nephropathy to employ oral steroid therapy, especially in moderate doses, to modify the course of CKD in a safe and effective manner,” Dr. Glassock adds. Additionally, the randomized controlled trial study design does well to minimize risk for bias, particularly confounding bias. A primary limitation of this work is the dose reduction, which took place midway through the trial for safety reasons, which although necessary, may have reduced the efficacy of blinding and certainly reduced trial consistency.

Originally Published By 2 Minute Medicine®. Reused in Physician’s Weekly with permission. ©2022 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.