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Changes in the size and electrophoretic mobility of HDL subpopulation particles in chronic kidney disease
Anna Gliwińska1, Agnieszka Ćwiklińska2, Monika Czaplińska3
1Department of Clinical Chemistry, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland.
Insights
Chronic kidney disease (CKD) alters high-density lipoprotein (HDL) particle size and mobility, potentially impairing its anti-atherogenic function. These changes correlate with kidney function decline and vary by HDL subpopulation.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Lipid Metabolism
Background:
- High-density lipoprotein (HDL) possesses anti-atherogenic properties but its metabolism is altered in chronic kidney disease (CKD).
- HDL's heterogeneous nature and subpopulation dynamics are crucial for understanding its function.
Purpose of the Study:
- To investigate alterations in HDL subpopulation particle size and electrophoretic mobility in non-dialysis CKD patients.
- To explore the relationship between these HDL changes and estimated glomerular filtration rate (eGFR).
Main Methods:
- Utilized non-denaturing two-dimensional polyacrylamide gradient gel electrophoresis (2D-PAGGE) to separate HDL subpopulations.
- Compared particle size and electrophoretic mobility of eight HDL subpopulations between 42 CKD patients (stages 3a-4) and 18 controls.
- Performed regression analysis to assess correlations with clinical parameters.
Main Results:
- CKD patients exhibited significantly smaller α-HDL and preβ2-HDL particle sizes compared to controls.
- Preβ2-HDL particles showed significantly higher relative electrophoretic mobility in CKD patients.
- HDL subpopulation size and mobility strongly correlated with eGFR, independent of other clinical factors.
Conclusions:
- Chronic kidney disease significantly impacts HDL particle size and mobility, suggesting potential HDL dysfunction.
- The observed changes in HDL subpopulations vary with CKD stage, indicating differential effects on HDL metabolism.
- These findings highlight the complex interplay between kidney disease and lipoprotein metabolism.
Background:
High-density lipoprotein (HDL) is a heterogeneous group of particles with anti-atherogenic properties whose metabolism is alterated in chronic kidney disease (CKD). The aim of this study was to evaluate the particle size and mobility of HDL subpopulations in non-dialysis CKD patients.
Methods:
The study involved 42 non-dialysis CKD patients (stages 3a-4) and 18 control subjects. HDL was separated by non-denaturing two-dimensional polyacrylamide gradient gel electrophoresis (2D-PAGGE) and eight HDL subpopulations; preβ1, preβ2a-c, and α1-4 were distinguished. The size and electrophoretic mobility of HDL subpopulation particles were compared between the groups, and a regression analysis was conducted.
Results:
In CKD patients, the mean sizes of α-HDL and preβ2-HDL particles were significantly lower compared to the control group (8.42 ± 0.32 nm vs. 8.64 ± 0.26 nm, p = 0.014; 11.45 ± 0.51 vs. 12.34 ± 0.78 nm, p = 0.003, respectively). The electrophoretic mobility of preβ2-HDL relative to α-HDL was significantly higher in CKD patients compared to the control group (Rf 0.65 ± 0.06 vs. 0.53 ± 0.10, p = 0.002). The size and mobility of HDL subpopulations correlated with eGFR values (p < 0.01). These relationships remained statistically significant after adjusting for age, gender, statin treatment, apolipoprotein AI, total cholesterol, and triglyceride levels.
Discussion:
CKD affects the size and mobility of HDL particles, which can be related to HDL dysfunction. The magnitude of HDL size and mobility changes depended on CKD stage and differed for individual HDL subpopulations, which indicates that some stages of HDL metabolism may be more affected by the presence of chronic kidney disease.
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