A review proposes a stage-based approach to IgA nephropathy (IgAN) that uses hematuria alongside proteinuria and eGFR to distinguish active immune-mediated disease from later structural kidney damage. The authors describe an immunologically active stage characterized by both proteinuria and hematuria, reflecting ongoing glomerular inflammation from galactose-deficient IgA1 immune-complex deposition and complement activation, and a later stage in which hematuria has resolved but proteinuria persists because of glomerulosclerosis and nephron loss. In an analysis of approximately 900 patients with IgAN, those with similarly high, stable proteinuria had more than twice the 4-year risk of a ≥50% decline in eGFR when hematuria was also present, supporting hematuria as a potential marker of disease activity and prognosis.
This framework could eventually help clinicians better match therapy to disease biology. In patients with persistent hematuria and proteinuria, treatments targeting abnormal IgA production or complement-mediated inflammation may be appropriate, whereas patients with proteinuria without hematuria may benefit primarily from therapies focused on slowing CKD progression. Patients with more advanced CKD and evidence of both active inflammation and chronic structural damage may require strategies addressing both processes. The authors emphasize that reducing proteinuria remains an important treatment goal, but they argue that its clinical meaning may differ depending on whether hematuria is present. Incorporating hematuria into assessment could therefore provide additional context for staging IgAN and selecting treatment as the number of mechanism-specific therapies continues to expand.
Reference: Suzuki Y. Principles for optimal drug selection in IgA nephropathy—time for integrating pathogenesis and clinical markers to guide therapy. Nephrology (Carlton). 2026 Feb;31(2):e70168. doi: 10.1111/nep.70168. PMID: 41655978; PMCID: PMC12883291.
