AI Article Synopsis

  • Immunoglobulin A nephropathy (IgAN) is the most common type of kidney inflammation globally, with recent research highlighting the critical role of the complement system, especially the alternative pathway, in its progression.
  • Studies indicate that specific proteins like factor H-related proteins and the lectin pathway contribute to disease severity, and glomerular deposition of markers like C3 and C4d may predict worse outcomes.
  • The understanding of complement's involvement in IgAN has led to the development of new treatments targeting various components of the complement system, with several clinical trials currently underway to assess their effectiveness.

Article Abstract

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent years have witnessed significant improvements in the understanding of the pathogenesis of IgAN and particularly, the pathogenic role of complement activation. The alternative complement pathway is the major complement cascade activator in IgAN, and glomerular C3 deposition has been shown to correlate with disease progression. In addition, several studies have provided insight into the pathogenic role of factor H-related proteins -1 and -5 in IgAN, as independent players in complement dysregulation. The lectin pathway has also been shown to be associated with the severity of IgAN. Glomerular deposition of C4d has been associated with increased histologic disease activity, faster decline in estimated glomerular filtration rate and higher risk of kidney failure. On the other hand, although overlooked in the Oxford classification, numerous studies have shown that the coexistence of thrombotic microangiopathy in IgAN is a significant indicator of a poorer prognosis. All the breakthroughs in the understanding of the contributing role of complement in IgAN have paved the way for the development of new complement-targeted therapies in this disease. Several ongoing trials are evaluating the efficacy of new agents against factor B (iptacopan, Ionis-FB-L), C3 (pegcetacoplan), factor D (vemircopan, pelecopan), C5 (ravulizumab, cemdisiran) and C5a receptor 1 (avacopan). In this study, we provide a comprehensive review of the role of complement in IgAN, including the emerging mechanisms of complement activation and the promising potential of complement inhibitors as a viable treatment option for IgAN.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695513PMC
http://dx.doi.org/10.1093/ckj/sfad198DOI Listing

Publication Analysis

Top Keywords

role complement
12
igan
9
pathogenic role
8
complement
8
complement activation
8
igan glomerular
8
glomerular deposition
8
complement igan
8
targeting complement
4
complement iga
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!