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Association of Small HDL Subclasses with Mortality Risk in Chronic Kidney Disease.

Julia T Stadler1,2, Andrea Borenich3, Anja Pammer1

  • 1Division of Pharmacology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria.

Antioxidants (Basel, Switzerland)
|January 8, 2025
PubMed
Summary

Reduced levels of small and extra-small high-density lipoprotein (HDL) subclasses, particularly XS-HDL-ApoA-II, are linked to higher mortality risk in chronic kidney disease (CKD) patients. This finding highlights HDL subclasses as potential prognostic markers for CKD outcomes.

Keywords:
HDL subclassesapolipoproteinschronic kidney diseaselipoproteinsmortalitysurvival

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Area of Science:

  • Cardiovascular Research
  • Nephrology
  • Biochemistry

Background:

  • High-density lipoproteins (HDL) comprise diverse subclasses with varying functional properties.
  • Smaller HDL particles exhibit potent anti-oxidative and anti-inflammatory effects.
  • The role of specific HDL subclasses in chronic kidney disease (CKD) progression and mortality remains incompletely understood.

Purpose of the Study:

  • To investigate the association between HDL subclass composition and all-cause mortality in patients with CKD.
  • To identify specific HDL subclasses or components that serve as prognostic markers for mortality in CKD.

Main Methods:

  • Nuclear magnetic resonance (NMR) spectroscopy was employed to analyze HDL subclass distribution in 463 CKD patients (stages 2-4).
  • Patient mortality data were collected over a mean follow-up period of 5.0 years.
  • Multivariable Cox regression and receiver operating characteristic (ROC) analyses were performed to assess associations with mortality.

Main Results:

  • Deceased patients had significantly lower levels of cholesterol, ApoA-I, and ApoA-II in small and extra-small (XS) HDL subclasses compared to survivors.
  • Reduced levels of XS-HDL-cholesterol, XS-HDL-ApoA-I, and XS-HDL-ApoA-II were independently associated with increased mortality risk.
  • XS-HDL-ApoA-II emerged as the most potent prognostic marker for mortality.

Conclusions:

  • Diminished levels of small and XS-HDL subclasses are strongly linked to elevated all-cause mortality in CKD patients.
  • Assessment of HDL subclass distribution, particularly XS-HDL-ApoA-II, offers valuable clinical insights for risk stratification in CKD.
  • Targeting small HDL subclasses may represent a future therapeutic strategy for improving outcomes in CKD.