Plasma complement proteins as biomarkers and therapeutic targets in chronic kidney disease: a Mendelian randomization

Yu-Peng Xu1,2, Zheng-Qi Song2, Ming-Li Chen1

  • 1Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou, Zhejiang, China.

Renal Failure
|July 17, 2025
PubMed

Insights

This study identifies specific plasma complement proteins as potential causal factors and biomarkers for Chronic Kidney Disease (CKD). These findings suggest new therapeutic targets for managing CKD and its progression.

Area of Science:

  • Immunology
  • Nephrology
  • Genetics

Background:

  • Chronic Kidney Disease (CKD) is a progressive condition with limited treatment options.
  • The complement system, a key immune network, is implicated in CKD pathogenesis.
  • Identifying reliable biomarkers for CKD onset and progression is crucial for effective management.

Purpose of the Study:

  • To investigate the causal role of plasma complement proteins in CKD and its clinical subtypes.
  • To discover novel biomarkers for CKD diagnosis and progression.
  • To identify potential therapeutic targets within the complement system for CKD.

Main Methods:

  • Utilized two-sample Mendelian randomization (MR) to analyze causal relationships.
  • Examined 28 plasma complement proteins against CKD outcomes using large-scale genetic datasets (FinnGen R11, CKDgen, 35,559 Icelandic individuals).
  • Performed protein-protein interaction and Gene Ontology (GO) enrichment analyses to explore biological pathways.

Main Results:

  • Identified 19 plasma complement proteins with causal links to CKD, with 6 remaining significant after correction.
  • CR1 and CFD showed significant associations with CKD risk and specific subtypes (membranous and diabetic nephropathy).
  • Complement proteins like CD55, C6, CR2, CFHR2, and CFD correlated with indicators of kidney function.

Conclusions:

  • Plasma complement proteins serve as promising biomarkers and therapeutic targets for CKD.
  • The study highlights the critical role of complement activation in CKD progression.
  • Findings support potential clinical applications in early CKD diagnosis, risk stratification, and treatment strategies.
Abstract

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