An update on corticosteroid treatment for IgA nephropathy

Malak Ghaddar, Jonathan Barratt, Sean J. Barbour

The use of corticosteroids to treat IgA nephropathy (IgAN) has been limited by many controversies related to uncertain benefit and safety concerns. Recent trials have tried to address these limitations. After being paused because of an excess of adverse events in the full-dose steroid arm, the TESTING trial compared a reduced dose of methylprednisolone to placebo in patients with IgAN after optimization of supportive therapy. Steroid treatment was associated with a significant reduction in the risk of a 40% decline in estimated glomerular filtration rate (eGFR), kidney failure and kidney death as well as a sustained decrease in proteinuria compared with placebo. Serious adverse events were more frequent with the full dose regimen but less common in the reduced dose regimen. A phase III trial evaluating a new formulation of targeted-release budesonide showed a significant reduction in short-term proteinuria and has resulted in accelerated FDA approval for use in the United States. In a subgroup analysis of DAPA-CKD trial, sodium-glucose transport protein 2 inhibitors reduced the risk of kidney function decline in patients who have completed or are not eligible for immunosuppression. Both reduced-dose corticosteroids and targeted-release budesonide are new therapeutic options that can be used in patients with high-risk disease. More novel-targeted therapies with a better safety profile are currently under investigations.