<p>As seen at <strong>Kidney Week 2025</strong>, therapeutic advancements in IgA nephropathy (IgAN) continue to emerge at a rapid pace. Conference participants expressed the sense of the field’s entrance into a new era in IgAN management.</p> <p><br></p> <p><em>Following these presentations, featured expert Pietro A. Canetta, MD, MS, was interviewed by </em>Conference Reporter<em> Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr Canetta on these findings are presented here.</em></p>

The approach to treating IgAN is rapidly evolving. The dream is to have a personalized treatment paradigm where you can analyze a patient’s biology to determine aspects of their treatment—to see whether, for example, complement activation is playing more or less of a role, based on the patient’s genetic signatures or potentially even the patient’s own immune complex profile by blood or urine assays. Of course, we are not there yet, but the future is bright.

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At Kidney Week 2025, we had 2 positive phase 3 trials reported in IgAN (ie, the VISIONARY [abstract SA-OR086] and ORIGIN 3 trials), and multiple promising agents are in development. Based on what we are seeing on the horizon, I think one important takeaway is that you cannot stop paying attention, because things are moving quickly. Many patients with IgAN are very proactive and belong to patient communities such as the IgA Nephropathy Foundation and/or the National Kidney Foundation (NKF). And, as news becomes a part of ongoing conversations on IgAN, it is likely that some patients will start to reach out to their health care providers with questions. Not long after the conference, we learned that the APRIL inhibitor sibeprenlimab received accelerated US Food and Drug Administration (FDA) approval based on the reduction of proteinuria. We are rapidly approaching a point where 2, 3, or even 4 new drugs could be FDA approved in the next few years. So, I think that it will be important to keep a close watch on these developments.

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There will be considerable interest in the APRIL- and BAFF-directed therapies among clinicians who treat patients with IgAN. I see this enthusiasm in my colleagues, for example, when thinking of patients for whom they are eager to try these newer agents, once FDA approved. This class of drugs offers a compelling combination of safety and efficacy—one that compares very favorably with existing treatments.

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We will also be watching closely for the data on glomerular filtration rate (GFR) from the VISIONARY and ORIGIN 3 trials. We have seen the positive phase 3 data on the surrogate end points of proteinuria and galactose-deficient IgA1, but we do not yet have the GFR data in hand, and our understanding is that this was at the FDA’s request. We do have some great-looking GFR data from phase 2 trials; however, presumably, the publication of the phase 3 GFR data will follow closely on the heels of any final determinations by the FDA. The ultimate goal is to show that you can prevent the loss of renal function, or GFR, and have fewer people progressing to end-stage kidney disease. This is a core concept that is emphasized in the recently updated version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on IgAN.

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For those at risk of progressive loss of kidney function, the new KDIGO guidelines recommend simultaneously considering treatment that addresses the immune-mediated aspects of IgAN and optimized supportive care. In that regard, historically, there has probably been some undertreatment of IgAN. There is good evidence that steroids do make a difference, as ultimately reported in the TESTING trial. However, messages emphasizing low-risk approaches (eg, RAS inhibitor or DEARA therapy ± SGLT2 inhibitor therapy focusing on generic responses to IgAN-induced nephron loss) have been resonating with many clinicians. This is all well and good, and low-risk approaches are valuable and appropriate, but they do not cure the disease. Despite the best-quality supportive care, many patients with IgAN progress, and some of them progress fairly quickly. And I think that we are now more cognizant of this.

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This has, therefore, induced somewhat of a paradigm shift from one of really remarkable conservatism—supportive care above all—to one of saying yes, we can actually use more aggressive treatments, including targeted and systemic steroids. We need to do better than what we were able to do in the past with just supportive care. Moreover, if we want to reap the most benefits, we really need to try to catch patients with IgAN earlier on, ideally before we start seeing changes in their kidney function, so that we can best protect the kidneys from permanent scarring damage.