Complement in acute kidney injury: a convergent pathogenic pathway in multifactorial renal damage

Area of Science:

• Nephrology
• Immunology
• Molecular Medicine

Background:

• Acute kidney injury (AKI) is a complex syndrome with diverse causes and overlapping injury pathways.
• Complement activation is increasingly recognized as a common factor in AKI pathogenesis, despite varying contributions across etiologies.

Purpose of the Study:

• To review the role of complement activation in AKI pathophysiology.
• To provide an integrative framework for understanding complement-mediated injury in AKI.
• To highlight potential for precision therapies targeting complement in AKI.

Main Methods:

• Review of preclinical models and clinical evidence on complement activation in AKI.
• Analysis of the mechanisms by which complement contributes to kidney injury.
• Synthesis of data on spatiotemporal heterogeneity and regulatory networks of complement in AKI.

Main Results:

• Complement activation, converging on C3 and C5, exacerbates AKI through inflammation, microcirculatory dysfunction, and tubular injury.
• The complement system orchestrates endothelial activation, leukocyte recruitment, and innate immune amplification in AKI.
• Dysregulation of complement regulators and crosstalk with other pathways amplify AKI progression.

Conclusions:

• Complement activation is a key convergent mechanism in multiple AKI etiologies.
• Targeting complement pathways, guided by biomarkers, may enable precision medicine approaches for AKI.
• Further research is needed to elucidate the precise role and therapeutic potential of complement modulation in AKI.