Corticosteroid

Oral Corticosteroids Increase Risk of Adverse Events in Patients With IgA Nephropathy

A recent study found that oral methylprednisolone is associated with an increased risk of infections and other adverse events in patients with immunoglobulin A (IgA) nephropathy and proteinuria of 1 g/d or greater.

Current guidelines recommend corticosteroid therapy for patients with IgA nephropathy and persistent proteinuria. However, the effects of the treatment on kidney function remain uncertain.
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The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was designed to recruit 750 patients with IgA nephropathy. However, only 262 patients were recruited. Patients were randomly assigned to receive either oral methylprednisolone (n = 136) or placebo (n = 126), with subsequent weaning over 4 to 6 months. Mean age was 38.6 years, and the majority of patients were men.

Patients who met the inclusion criteria had a proteinuria greater than 1 g/d and an 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.

The primary outcome was end-stage kidney disease, mortality due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were defined as serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events.

After a median follow-up of 2.1 years, recruitment was discontinued due to excess serious adverse events, mostly caused by serious infections. A total of 20 participants in the methylprednisolone group had experienced serious adverse events, compared with 4 in the placebo group. Results also indicated that 8 patients in the methylprednisolone group had experienced the primary renal outcome, compared with 20 in the placebo group.

“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,” the researchers concluded. “Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.”

—Christina Vogt

Reference:

Lv J, Zhang H, Wong MG, et al; the TESTING Study Group. Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: the TESTING randomized clinical trial. JAMA. 2017;318(5):432-442. doi:10.1001/jama.2017.9362.