IgA Nephropathy: An Overview of the Clinical Trials

IgA nephropathy (IgAN) is characterized by the deposition of poorly-O-galactosylated IgA1 (also referred to as galactose-deficient IgA1 or gd-IgA1) containing immune complexes in the glomerular mesangium. This triggers a variable degree of glomerular inflammation that leads to progressive kidney damage and often kidney failure. The acceptance of proteinuria reduction as a reasonably likely surrogate end point for treatment effects on progression to kidney failure has led to many clinical trials evaluating novel and repurposed therapies for IgAN. New treatments leverage different aspects of IgAN pathophysiology, including the modulation of mucosal immunity, mechanisms of B-cell activation, and complement activity. The approval of the first treatments evaluated specifically for IgAN (including delayed-release budesonide, sparsentan, atrasentan, and iptacopan) represent meaningful advancements in the management landscape, and promisingly, many more treatments seem poised to arrive. This review compiles a list of current active trials for IgAN and highlights the necessity for ongoing research to optimize therapeutic strategies to further improve outcomes for those living with IgAN.