Abstract

Many patients with IgA nephropathy (IgAN) progress to end-stage kidney disease even with optimal supportive care. An improved understanding of the pathophysiology of IgAN in recent years has led to the investigation of targeted therapies with acceptable tolerability that may address the underlying causes of IgAN or the pathogenesis of kidney injury. The complement system - particularly the lectin and alternative pathways of complement - have emerged as key mediators of kidney injury in IgAN and possible targets for investigational therapy. This review will focus on the lectin pathway. Examination of kidney biopsies has consistently shown glomerular deposition of mannan-binding lectin (one of six pattern-recognition molecules that activate the lectin pathway) together with IgA1 in up to 50% of patients with IgAN. Glomerular deposition of pattern-recognition molecules for the lectin pathway is associated with more severe glomerular damage and more severe proteinuria and hematuria. Emerging research suggests that the lectin pathway may also contribute to tubulointerstitial fibrosis in IgAN, and that collectin-11 is a key mediator of this association. This review summarizes the growing scientific and clinical evidence supporting the role of the lectin pathway in IgAN and examines the possible therapeutic role of lectin pathway inhibition for these patients.

View details for DOI 10.1016/j.kint.2023.04.029

View details for PubMedID 37263354