Navigating novel therapeutics for IgA nephropathy: literature review

Abstract IgA nephropathy guidelines are evolving, yet not rapidly enough to keep pace with advances in pathophysiology, diagnostics, and therapeutics. The general understanding of the four-hit hypothesis still overlays the process of IgA nephropathy: formation of excessive galactose-deficient IgA1 (Gd-IgA1), formation of IgG/IgA anti-Gd-IgA1 antibodies, formation of circulating immune complexes, and deposition of these immune complexes with immunologic and endothelial injury to the glomerulus. On this background, questions of genetic susceptibility, clinical course, waxing/waning disease, differential pathology and response to therapy in different populations, healthcare costs, and infection vs. end-stage renal disease risk populate the research landscape. Over the last 9–10 years, several new therapies have been tested and, in many cases, approved by the U.S. Food and Drug Administration (FDA). This has resulted in what was once a simple-to-understand renal disease, readily at the reach of most nephrologists, now becoming the vanguard of the molecular precision medicine revolution currently gripping nephrology. New advances in molecular therapeutics, genetics, pharmacology, and biological therapy have made IgA nephropathy a disease that requires the attention of nephrologists with training in glomerular diseases who have a facile familiarity with biological therapy and immunology. This review aims to serve as a thorough guide to perplexed physicians hoping to place IgA nephropathy back in the control of the clinician nephrologist. Clinical trial number: Not applicable