Can Urinary Complement Proteins Stratify Patients to Therapeutic Complement Inhibitors?

Medjeral-Thomas, Nicholas

doi:10.1016/j.ekir.2022.03.024

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…In addition to the prognostic implications of complement deposits, plasma levels of complement proteins, regulators and complement activation products could become valuable biomarkers of clinical application in IgAN. The urinary excretion of complement factors could also be a useful biomarker to monitor complement activation in glomerular diseases [ 40 , 41 ], although conclusive studies are needed in this regard.…”

Section: Role Of Complement In Igan Pathogenesismentioning

confidence: 99%

Targeting complement in IgA nephropathy

Caravaca-Fontán,

Gutiérrez,

Sevillano

et al. 2023

Clinical Kidney Journal

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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-LRX), 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.

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Section: Role Of Complement In Igan Pathogenesismentioning

confidence: 99%