Expert consensus on the likelihood and treatment of high- and low-inflammatory activity Immunoglobulin A nephropathy

Abstract Purpose Immunoglobulin A nephropathy (IgAN) is characterized by glomerular deposition of immunoglobulin A, with current treatments focused on controlling disease activity and slowing progression. In the context of expanding therapeutic options, this expert panel aimed to provide guidance on defining and managing high- and low-inflammatory activity IgAN phenotypes. Methods A modified Delphi panel was conducted with eleven US-based nephrologists and pathologists. Participants completed two rounds of online surveys followed by an in-person meeting. Clinical scenarios were rated and analyzed using the RAND/UCLA Appropriateness Method and each were classified as appropriate, inappropriate, or uncertain. Outcomes included consensus on the likelihood of high- versus low-inflammatory activity IgAN, appropriateness of therapies, and the timing of complement inhibitor initiation relative to meningococcal B vaccination. Results The panel reached agreement on 92% of scenarios. High-inflammatory activity IgAN was characterized by hematuria, moderate- to high-grade proteinuria, and inflammatory histology, whereas low-inflammatory activity IgAN was characterized by absence of hematuria, low-grade proteinuria, stable eGFR, and inactive histology. Panelists more frequently supported adding therapies beyond RAAS ± SGLT2 inhibitors for high- versus low-inflammatory activity IgAN. Complement inhibitor initiation was considered appropriate at any point during the meningococcal B vaccination series when antibacterial prophylaxis was administered concurrently. Conclusions This guidance offers practical recommendations for managing patients with high- and low-inflammatory activity IgAN. As therapeutic options continue to expand, ongoing research and updated consensus efforts will be essential to support decision-making. In light of new KDIGO guidelines, we believe these phenotypes can assist clinicians until more direct biomarkers are identified. Data Sharing All data are included in the manuscript and/or supporting information.