Systemic and targeted steroids for the treatment of IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is a common glomerulonephritis partially correlated with mucosal immune system dysfunction. Progressive renal failure occurs in many patients, with about 30-50% of the patients with IgAN developing end-stage kidney disease (ESKD). Many treatments have been used for decades, despite uncertainty about their effectiveness and the ideal dose. Randomised controlled trials reported that systemic glucocorticoids can be an effective treatment for patients with persistent and significant proteinuria despite renin-angiotensin system inhibitors use possibly causing systemic side effects. The primary focus of IgAN management should be based on optimised supportive care, including renin-angiotensin system (RAS) blockade and now SGLT2 inhibitors. The novel targeted-release formulation (TRF) of budesonide has been tested to reduce the adverse events of systemic steroids by delivering the drug to the distal ileum. The local efficacy of TRF-budesonide may represent a novel and promising approach to treating IgAN. Two clinical trials showed that TRF-budesonide could significantly reduce proteinuria and haematuria and possibly preserve renal function while significantly reducing the side effects. However, the limited number of treated patients and the relatively short follow-up suggest caution before considering budesonide superior to the current six-months steroid pulses scheme. Long-term data on the efficacy and safety of TRF budesonide are awaited, together with the design of trials with a head-to-head comparison with systemic steroids before considering TRF-budesonide as the standard of care treatment for IgAN nephropathy.