Management of IgA nephropathy and the expanding role of immunomodulation

IgA nephropathy (IgAN) requires effective long-term management to avoid kidney failure. Proteinuria and reductions in estimated glomerular filtration rate are important clinical markers of progression, and they are established surrogate efficacy outcomes in clinical trials of new and emerging IgAN therapies. Despite optimized supportive care (including lifestyle modification and renin–angiotensin system inhibition) as a mainstay of IgAN management, many patients will still develop kidney failure, and the concept of "disease modification" refers to interventions that prevent irreversible kidney damage. Disease-modifying therapies may include IgAN-specific and anti-inflammatory strategies, whereas supportive care encompasses interventions that address generic mechanisms of nephron loss and interstitial injury that lead to chronic kidney disease. Targeted therapies, such as Nefecon (targeted-release formulation budesonide) and iptacopan, which address the immune-mediated pathogenic triggers of nephron loss, are important additions. Lifestyle modification, renin–angiotensin system inhibition, sodium-glucose cotransporter-2 inhibitors, and newer agents, such as sparsentan and atrasentan, are also available to manage the generic responses to IgAN-induced nephron loss common to many forms of proteinuric chronic kidney disease. As our understanding of the pathogenic mechanisms underlying disease progression in IgAN has expanded, so has the recognition that IgAN-specific, targeted immunomodulatory therapies are needed, and that these can be used in combination with other agents addressing the more generic causes of nephron loss. These approaches together can help to modify the course of the disease in patients and avoid progression to kidney failure.