Emerging perspectives in the management of IgA nephropathy: a comprehensive review.

Abstract

IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and renal failure. This disorder is characterized by the deposition of immune complexes containing galactose-deficient forms of IgA and complement C3 in the glomeruli. Until now, disease management relied mainly on optimized supportive care. Systemic corticosteroid therapy is proposed for patients at high risk of disease progression, but the effectiveness and safety of this approach are under debate. A significant proportion of patients do not respond to current therapies and require kidney replacement therapy at a young age, with substantial costs and impact on quality of life. Recently, there have been multiple joint efforts to improve the understanding of IgAN pathophysiology. International collaborations resulted in multiple ongoing clinical trials that are providing new insights toward innovative therapeutic options such as SGLT2 inhibitors, dual endothelin and angiotensin receptor blockers, targeted-release budesonide, B-cell proliferation and differentiation inhibitors, and complement system blockers. Based on this new evidence, revision of the guidelines to manage IgAN is expected to occur in the near future. In addition to the novelty in therapeutic agents, there is also a growing interest in new noninvasive biomarkers for IgAN screening, risk stratification to monitor the course of the disease, and the response to treatment. In this review, we discuss current knowledge on the pathophysiology of IgAN, disease management, and emerging advances in clinical translation of IgAN research.