IgA nephropathy management: what does the future hold?

Increased understanding of the pathogenesis of IgA nephropathy (IgAN) has led to the development of new investigational agents tailored to this disease. The identification of surrogate markers of early treatment benefit has facilitated regulatory approval of these novel therapies. The surge in available data from several completed trials has prompted the recent revision of the Kidney Disease: Improving Global Outcomes guidelines for IgAN. Two agents have been fully approved for use in patients with IgAN in some regions: Nefecon, an oral targeted-release formulation of budesonide, and sparsentan, a dual endothelin A and angiotensin II receptor antagonist. Iptacopan and atrasentan are conditionally approved on the basis of proteinuria data; full approval will be evaluated once data on kidney function are available. With the potential future expansion of the IgAN treatment armamentarium, a dual approach to IgAN management is highly likely, addressing the overproduction of galactose-deficient IgA1 and downstream consequences of deposition of nephritogenic immune complexes, as well as considering supportive strategies targeting common non-disease-specific ongoing nephron loss. Combination therapies with different classes of drugs will likely become the new standard of care for chronic kidney disease as they target distinct pathogenic mechanisms or "hits" (namely, hemodynamic, immune, galactose-deficient IgA1-generating, inflammatory, and fibrotic processes involved in IgAN and chronic kidney disease progression). To improve personalized care for patients with IgAN, further research is needed to identify and validate noninvasive biomarkers for diagnosis, prognosis, treatment selection, and monitoring response.