2025/01/31 by Jürgen Floege, Amélie Bernier-Jean, Jonathan Barratt +1 · 1 voice · 5 citations
Medicine · #Autoimmune Bullous Skin Diseases #Chronic Lymphocytic Leukemia Research #Renal Diseases and Glomerulopathies
paper · doi:10.1016/j.kint.2025.01.014
openalex publication_date 2025/01/31 · openalex created_date 2025/02/01 · openalex updated_date 2026/07/31
IgA nephropathy (IgAN), the world's most common primary glomerular disease, carries a significant lifetime risk for kidney failure as well as an enormous socioeconomic burden. In the past, studies in patients with IgAN largely focused on optimizing so-called supportive care, that is, blockade of the renin-angiotensin system, blood pressure control, and lifestyle modifications. The effectiveness of immunosuppressive measures, particularly high-dose corticosteroid therapy, has been reported variably, but there is considerable evidence for an increase in serious adverse effects with such therapies. This disappointing situation has changed dramatically with a better understanding of the pathogenesis of IgAN, and with regulatory agencies accepting changes in proteinuria and the estimated glomerular filtration rate loss or slope over 2 to 3 years as surrogate outcome markers. A multitude of new therapies are now being evaluated in IgAN, and several drugs, such as sodium-glucose transporter-2 inhibitors, sparsentan (a dual endothelin-1 and angiotensin II receptor blocker), nefecon (a targeted release formulation of budesonide), and iptacopan (a complement factor B inhibitor), have been approved, with more to come in the next few years. In this review, we propose a new treatment paradigm that combines therapies with different mechanisms of action to target the immune components and the chronic kidney disease components of IgAN in parallel to preserve long-term kidney survival.