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Updated: May 25, 2025

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
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Urine complement analysis implies complement activation is involved in membranous nephropathy.

Yingxue Xu1,2, Yi Li1, Yong Zhang3

  • 1Department of Nephrology and Nephrology Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Frontiers in Medicine
|February 28, 2025
PubMed
Summary
This summary is machine-generated.

This study reveals that urinary complement abnormalities in membranous nephropathy (MN) can predict clinical remission and disease progression. These findings highlight complement proteins as potential biomarkers for guiding targeted therapies in MN patients.

Keywords:
clinical remissioncomplementhistopathologymembranous nephropathyproteomics

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Area of Science:

  • Nephrology
  • Immunology
  • Proteomics

Background:

  • Membranous nephropathy (MN) onset and progression are linked to complement activation, but kidney-specific characteristics remain unclear.
  • Investigating urine proteomic data offers a novel approach to understand complement activation features in MN.
  • Understanding complement component relationships with clinical factors is crucial for managing MN.

Purpose of the Study:

  • To investigate complement activation features in membranous nephropathy (MN) using urine proteomic data.
  • To examine the relationship between urinary complement components, clinicopathological features, and clinical outcomes in MN patients.
  • To identify potential urinary biomarkers for predicting clinical remission and guiding therapy in MN.

Main Methods:

  • Differential expression protein (DEP) analysis of urine samples from MN patients, IgA nephropathy (IgAN) patients, and healthy controls (HC).
  • Gene Ontology and KEGG pathway analyses on DEPs in MN.
  • Validation of 11 complement proteins and assessment of CD59 and C5b-9 expression in renal tissues using immunohistochemistry and immunofluorescence.

Main Results:

  • 1,427 DEPs identified between MN and HC groups, with significant enrichment in the complement-activated pathway in MN.
  • Correlation found between proteinuria and 27 urinary complement proteins; Collectin12 and C1s linked to tubular atrophy/interstitial fibrosis and monocyte infiltration.
  • Urinary CD59 predicted clinical remission; lower C5b-9 deposition and higher CD59 expression observed in the remission group.

Conclusions:

  • Abnormal urinary complement component levels are common in MN.
  • Complement abnormalities can serve as clinical biomarkers for tracking MN progression and predicting remission.
  • Findings support the potential for targeted complement therapy guided by urinary biomarkers in MN.