Targeted-Release Budesonide in IgA Nephropathy: A Gut–Kidney–Focused Therapeutic Strategy

In Targeted-Release Budesonide in IgA Nephropathy: A Gut–Kidney–Focused Therapeutic Strategy, our experts delve into the following critical questions:

How does targeted-release budesonide different from systemic corticosteroids in terms of both mechanism of action (reducing Gd-IgA) and delivery?

What makes this approach more selective or safer from a gut-kidney perspective?

Led by the Dr. Appel, Dr. Sanchez Russo discusses how targeted-release budesonide differs from systemic corticosteroids by acting primarily within the gut-associated lymphoid tissue, a key site of aberrant IgA production in IgA nephropathy. By delivering budesonide to the distal ileum, this formulation reduces the production of galactose-deficient IgA (Gd-IgA) at its source, rather than broadly suppressing the immune system. In contrast, systemic corticosteroids exert widespread immunosuppressive effects, which can reduce inflammation but are associated with significant off-target toxicity. The targeted-release design allows budesonide to undergo extensive first-pass hepatic metabolism, resulting in lower systemic exposure and fewer steroid-related adverse effects. This gut-focused mechanism supports the emerging gut–kidney axis concept in IgAN, linking mucosal immune dysregulation to downstream glomerular injury. From a safety perspective, this selectivity may translate into a more favorable risk–benefit pr

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

Our next episode, Positioning Emerging Targeted Therapies in the Evolving IgA Nephropathy Treatment Paradigm, further explores IgA nephropathy, highlighting how endothelin receptor antagonists, complement inhibitors, and novel agents such as BAFF/APRIL pathway blockers are being incorporated into clinical practice based on disease activity, residual risk, and response to foundational therapy. It highlights practical considerations for sequencing these therapies as part of a more personalized, mechanism-driven approach to IgAN management.