Reduced-Dose Methylprednisolone Boosts Kidney Health in High-Risk IgAN but Increases SAEs: TESTING analysis

The study, published in Kidney International Reports, also noted that the reduced-dose regimen is associated with a modestly higher number of serious adverse events (SAEs) compared to placebo.

"Results indicated that a 0.4 mg/kg/d methylprednisolone regimen is linked to a 76% reduction in the risk of the primary composite kidney outcome compared to supportive care alone. Additionally, the study highlighted that this treatment delays the progression to kidney failure in patients already receiving maximal supportive care," the researchers reported.

The global TESTING study found that methylprednisolone lowers the risk of major kidney events in high-risk IgAN patients compared to supportive care alone, though it is linked to a higher incidence of SAEs, particularly with full-dose therapy. In the prespecified analysis of the reduced-dose cohort from the TESTING trial, Dana Kim, The George Institute for Global Health, University of New South Wales, Sydney, Australia, and colleagues evaluated the risk-benefit balance of the reduced-dose methylprednisolone regimen.

Patients with IgAN, proteinuria ≥1 g/d despite three months of renin-angiotensin-system blockade, and estimated glomerular filtration rate (eGFR) of 30 to 120 ml/min per 1.73 m2 were included between 2017 and 2019. They were randomized to reduced-dose methylprednisolone 0.4 mg/kg/d or placebo. The primary outcome was a composite of a 40% decline in eGFR, kidney failure, or mortality due to kidney disease.

The researchers reported the following findings:

• Two hundred and forty-one participants were randomized and followed for a median of 2.5 years (mean age: 37 years; baseline eGFR: 65 ml/min per 1.73 m2; proteinuria: 2.48 g/d).
• Methylprednisolone was associated with fewer primary outcome events compared to placebo (7/121 versus 22/120; hazard ratio [HR]: 0.24), lowered proteinuria, and reduced eGFR rate of decline from baseline.
• The mean difference between methylprednisolone and placebo in proteinuria and eGFR from baseline was −1.15 g/d and 7.9 ml/min per 1.73 m2 at 12 months, respectively; however, these benefits were lost over time.
• There were seven versus 3 SAEs in the methylprednisolone versus placebo group (HR: 1.97), including five versus two infections.

Reduced-dose methylprednisolone is effective in enhancing kidney outcomes for high-risk IgAN patients; however, it is associated with a modest increase in serious adverse events (SAEs) compared to placebo, the researchers concluded.

Reference:

Kim, D., Lv, J., Hladunewich, M., Jha, V., Hooi, L. S., Monaghan, H., Shan, S., Reich, H. N., Barbour, S., Billot, L., Zhang, H., Perkovic, V., & Wong, M. G. (2024). The Efficacy and Safety of Reduced-Dose Oral Methylprednisolone in High-Risk Immunoglobulin A Nephropathy. Kidney International Reports, 9(7), 2168-2179. https://doi.org/10.1016/j.ekir.2024.03.032