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Updated: Apr 7, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
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.
Background:
The reduced glomerular filtration rate in the advanced stages of chronic kidney disease (CKD) leads to plasma accumulation of uraemic retention solutes including proteins. It has been hypothesized that these changes may, at least in part, be responsible for CKD-associated morbidity and mortality. However, most studies focused on the role of individual proteins, while a holistic, large-scale, integrative approach may generate significant additional insight.
Methods:
In a discovery study, we analysed the plasma proteome of patients with stage 2-3 CKD (n = 14) and stage 5 CKD with haemodialysis (HD) (n = 15), using high-resolution LC-MS/MS analysis. Selected results were validated in a cohort of 40 patients with different CKD stages with or without HD, using ELISA.
Results:
Of a total of 2054 detected proteins, 127 displayed lower, while 206 displayed higher abundance in the plasma of patients on HD. Molecular pathway analysis confirmed the modification of known processes involved in CKD complications, including decreased haemostasis and increased inflammation, complement activation and vascular damage. In addition, we identified the plasma increase during CKD progression of lysozyme C and leucine-rich alpha-2 glycoprotein, two proteins related to vascular damage and heart failure. High level of leucine-rich alpha-2 glycoprotein was associated with higher mortality in stage 5 CKD patients on HD.
Conclusions:
This study provides for the first time a comprehensive assessment of CKD plasma proteome, contributing to new knowledge and potential markers of CKD. These results will serve as a basis for future studies investigating the relevance of these molecules in CKD associated morbidity and mortality.
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