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

High-density lipoproteins (HDL) exist in various subclasses, with smaller HDL particles possessing the highest anti-oxidative and anti-inflammatory properties. Understanding the role of these specific subclasses in chronic kidney disease (CKD) could provide valuable insights into disease progression and potential therapeutic targets. In the present study, we assessed HDL subclass composition in 463 patients with CKD stage 2-4 using nuclear magnetic resonance spectroscopy. Over a mean follow-up period of 5.0 years, 18.6% of patients died. Compared to survivors, deceased patients exhibited significantly lower levels of cholesterol, ApoA-I, and ApoA-II within the small and extra-small (XS) HDL subclasses. Multivariable Cox regression analysis, adjusted for traditional cardiovascular and renal risk factors, demonstrated that reduced levels of XS-HDL-cholesterol, XS-HDL-ApoA-I, and XS-HDL-ApoA-II were independently associated with an increased risk of mortality. Furthermore, receiver operating characteristic analysis identified XS-HDL-ApoA-II as the most potent prognostic marker for mortality. In conclusion, reduced small and XS-HDL subclasses, especially XS-HDL-ApoA-II, are strongly associated with increased all-cause mortality risk in CKD patients. Assessment of HDL subclass distribution could provide valuable clinical information and help identify patients at high risk.