Dysfunctional high-density lipoproteins in children with chronic kidney disease

Abstract

Objectives Our aim was to determine if chronic kidney disease (CKD) occurring in childhood impairs the normally vasoprotective functions of high-density lipoproteins (HDL). Materials and Methods HDL were isolated from children with end-stage renal disease on dialysis (ESRD), children with moderate CKD and controls with normal kidney function. Macrophage response to HDL was studied as expression of inflammatory markers (MCP-1, TNF-α, IL-1β) and chemotaxis. Human umbilical vein endothelial cells were used for expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and adhesion. Cellular proliferation, apoptosis, and necrosis of endothelial cells was measured by MTS/PMS reagent-based assay, flow cytometry, and ELISA. Cholesterol efflux was assessed by gas chromatographic measurements of cholesterol in macrophages exposed to HDL. Results Compared with HDLControl, HDLCKD and HDLESRD heightened the cytokine response and disrupted macrophage chemotaxis. HDLControl reduced endothelial expression of ICAM-1, VCAM-1, E-selectin, whereas HDLCKD and HDLESRD were less effective and showed reduced capacity to protect endothelial cells against monocyte adhesion. Compared with a dramatically enhanced endothelial proliferation following injurious stimulus by HDLControl, neither HDLCKD nor HDLESRD caused proliferative effects. HDL of all three groups were equally protective against apoptosis assessed by flow cytometry and cleaved caspase-3 activity. Compared to HDLControl, HDLCKD and HDLESRD trended toward reduced capacity as cholesterol acceptors. Conclusion CKD in children impairs HDL function. Even in the absence of long-standing and concomitant risk factors, CKD alters specific HDL functions linked to control of inflammation and endothelial responses.

Molecular mechanisms of disorders of lipid metabolism in chronic kidney disease

“…There is also emerging evidence that advanced CKD and ESRD are not only associated with significantly reduced HDL anti-inflammatory activity, but in a subset of patients HDL paradoxically becomes proinflammatory in nature (116,117). This was shown in a series of studies which showed that HDL from hemodialysis patients had reduced antichemotactic activity and paradoxically stimulated production of inflammatory cytokine by immune cells (113,118). The pro-inflammatory characteristics of ESRD patients' HDL were found to be associated with presence of atherogenic protein content including lipoprotein enriched with serum amyloid A whose pro-inflammatory actions were demonstrated by in vitro experiments (119).…”

Progression of Chronic Kidney Disease Affects HDL Impact on Lipoprotein Lipase (LPL)-Mediated VLDL Lipolysis Efficiency

“…HDL in CKD have reduced ability to promote cholesterol efflux from macrophages as well as HDL anti-oxidative, anti-inflammatory and vasoprotective properties are impaired [8,10]. Lipid and lipoprotein disturbances develop in the early stages of the disease and exaggerate with the progression of renal failure.…”

Metabolic Syndrome and Smoking Are Associated with Future Development of Advanced Chronic Kidney Disease in Older Adults

“…Furthermore, most prior studies investigating the association between CKD and MetS components have been cross-sectional [10,11,12]. In addition, these studies provide results for one or two racial/ethnic groups: Chen et al [13], Hou et al [10], and Zhang et al [11] included only Asians; Kurella et al [9] had a black and white sample.…”

“…In addition, these studies provide results for one or two racial/ethnic groups: Chen et al [13], Hou et al [10], and Zhang et al [11] included only Asians; Kurella et al [9] had a black and white sample. Also, most studies do not encompass the older-age groups: Kurella et al [9] only had middle-aged individuals between the ages of 45 and 64 years, and Kaseda et al [12] only had children between the ages of 1 and 18 years. Thus, most studies do not provide much evidence on how these associations affect an older cohort and much less on how these may be applicable to older-age multiethnic populations.…”