Aligning Treatment Goals in IgA Nephropathy: Applying KDIGO’s Dual-Pathway Framework to Clinical Decision-Making

Welcome back to another AJMC Insights series. In this episode titled, Aligning Treatment Goals in IgA Nephropathy: Applying KDIGO’s Dual-Pathway Framework to Clinical Decision-Making, Dr. Gerald Appel led the conversation about the following questions:

From your perspective, what are the primary treatment goals in IgAN today?

Can you explain how KDIGO’s dual-pathway approach (targeting immune complex formation + managing nephron loss) should guide treatment decisions?

Dr. Luis Sanchez Russo highlighted that IgA nephropathy (IgAN) management has evolved beyond a singular focus on slowing kidney function decline to a more comprehensive, mechanism-driven approach. Today, the primary treatment goals in IgAN center on reducing proteinuria, preserving long-term kidney function, minimizing disease progression to end-stage kidney disease, and improving patient quality of life. Achieving sustained reductions in proteinuria is a key surrogate marker of treatment success, as it closely correlates with long-term renal outcomes. Equally important is early risk stratification to identify patients most likely to progress, allowing for timely intervention before irreversible kidney damage occurs. Balancing efficacy with safety is also a central goal, particularly given the chronic nature of IgAN and the need for durable therapies with manageable tolerability profiles.

The KDIGO 2025 guidelines reinforce these goals through a dual-pathway treatment framework that addresses both upstream disease drivers and downstream consequences of kidney injury. The first pathway focuses on targeting immune complex formation and deposition, which are central to IgAN pathogenesis and ongoing inflammatory activity. Intervening here aims to reduce glomerular inflammation and prevent further structural damage. The second pathway emphasizes managing nephron loss and its clinical sequelae through optimized supportive care, including blood pressure control, renin-angiotensin system inhibition, and emerging therapies that slow chronic kidney disease progression.

Together, this dual-pathway approach encourages clinicians to individualize therapy based on disease activity and chronicity, rather than relying on a one-size-fits-all strategy. By simultaneously addressing immune-mediated injury and progressive nephron loss, clinicians can better align treatment decisions with the underlying biology of IgAN and the long-term needs of patients, ultimately aiming to modify disease trajectory rather than simply react to its consequences.

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

In the next episode, Integrating Risk Stratification and Supportive Care in IgA Nephropathy Management, panelists will continue their discussion on IgA nephropathy and highlight how histologic findings, including Oxford MEST-C scores, inform clinical decision-making as supportive rather than standalone determinants of therapy, while highlighting the foundational role of optimized supportive care. It also examines when escalation to disease-specific treatment is appropriate and how lifestyle interventions are incorporated to slow nephron loss, alongside real-world challenges in sustaining patient adherence.