New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome

Griet Glorieux1, William Mullen2, Flore Duranton3

  • 1Nephrology Section, Ghent University Hospital, Gent, Belgium.

Insights

Chronic kidney disease (CKD) alters plasma proteins, impacting health. This study identifies specific proteins, like leucine-rich alpha-2 glycoprotein, linked to vascular damage and mortality in CKD patients.

Area of Science:

  • Biochemistry
  • Nephrology
  • Proteomics

Background:

  • Reduced glomerular filtration rate in chronic kidney disease (CKD) causes accumulation of waste products.
  • CKD-associated morbidity and mortality may stem from these accumulated substances.
  • Previous research focused on individual proteins, necessitating a large-scale, integrated approach.

Purpose of the Study:

  • To comprehensively assess the plasma proteome in patients with varying stages of CKD.
  • To identify potential protein biomarkers associated with CKD progression and complications.
  • To explore the relationship between plasma protein changes and CKD-related outcomes.

Main Methods:

  • High-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze plasma proteomes.
  • Discovery study included patients with stage 2-3 CKD (n=14) and stage 5 CKD on hemodialysis (HD) (n=15).
  • Enzyme-linked immunosorbent assay (ELISA) validated findings in a larger cohort (n=40).

Main Results:

  • 2054 proteins were detected; 127 showed decreased and 206 increased abundance in HD patients.
  • Pathway analysis revealed altered hemostasis, inflammation, complement activation, and vascular damage.
  • Lysozyme C and leucine-rich alpha-2 glycoprotein levels increased with CKD progression, linked to vascular damage and heart failure.

Conclusions:

  • This study offers a comprehensive view of the CKD plasma proteome.
  • Identified proteins may serve as novel biomarkers for CKD.
  • Further research is warranted to confirm the role of these proteins in CKD morbidity and mortality.
Abstract

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