Authors of a review of the lectin complement pathway in IgA nephropathy (IgAN) highlights growing evidence that complement activation may contribute to kidney injury and progression in a subset of patients. Glomerular deposition of lectin-pathway components has been associated with greater proteinuria, lower eGFR, more severe histologic lesions, and poorer kidney outcomes. C4d is especially noteworthy as a potential biomarker: studies have linked both tissue and urinary C4d with disease progression, and urinary C4d may offer a noninvasive way to reflect kidney complement activity. However, these biomarkers are not yet sufficiently validated or standardized for routine clinical decision-making.
The therapeutic picture is more complicated. Lectin-pathway activation appears to occur in only about 15% to 25% of patients with IgAN, and the pathway may function more as an amplifier of kidney injury than as a universal disease driver. A phase 3 trial targeting MASP-2 failed to significantly reduce proteinuria. This underscores the potential interaction between the lectin and alternative complement pathways and the need to identify which patients are most likely to benefit from pathway-specific treatment. The authors conclude that better biomarkers and prospective validation will be essential to translate complement biology into more personalized risk assessment and treatment strategies.
Reference: Yu X, Gao H, Sun X. Research progress on the lectin pathway of complement in IgA nephropathy. Front Immunol. 2026 Feb 27;17:1757595. doi: 10.3389/fimmu.2026.1757595.
