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

Abstract

Background/Aims: Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency. Methods: VLDL was isolated from non-dialysis patients in CKD stages 3 and 4 and from non-CKD patients. The VLDL was incubated with LPL at the constant LPL:VLDL-TG ratio, in the absence or presence of HDL. After incubation, the VLDL was separated and the percentage (%) of hydrolyzed TG was calculated. Results: HDL presence increased the lipolysis efficiency of VLDL isolated from CKD and non-CKD patients, for the VLDL-TG> 50 mg/dl. Its effect was dependent on the VLDL-TG and HDL-cholesterol concentrations in the reaction mixtures: the higher the concentrations of VLDL-TG and HDL-cholesterol, the greater the effect. The positive impact of HDL on VLDL lipolysis was modified by CKD progression: the percentage of lipolyzed VLDL-TG in the presence of HDL decreased with a reduction in eGFR (r=0.43, p=0.009), and for patients with stage 4 CKD, no positive impact of HDL on lipolysis was observed. The percentage of lipolyzed TG correlated negatively with apoE and apoCs content in VLDL, and positively with HDL-apoCII, as well as with VLDL and HDL apoCII/ apoCIII ratios. The progression of CKD was associated with unfavourable changes in VLDL and HDL composition; apoE and apoCs levels increased in VLDL with a decrease in eGFR whereas the HDL-cholesterol level decreased. Conclusion: The progression of CKD affects lipoprotein composition and properties, and modulates the positive impact of HDL on VLDL lipolysis efficiency. In CKD patients, HDL deficiency and dysfunction can directly affect hypertriglyceridaemia development.

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

“…Oxidative modifications of HDL are thought to contribute to the formation of dysfunctional proinflammatory HDL. Moreover,Ćwiklińska et al [69] demonstrated that in CKD patients the positive effect of HDL on the efficiency of VLDL lipolysis was modified. They found that the efficacy of VLDL lipolysis in the presence of HDL was, in non-CKD patients, significantly higher than in those with CKD and it decreased with a reduction in estimated glomerular filtration rate (eGFR).…”

“…It seems that HDL disturbances in CKD play a key important role in retarded VLDL catabolism and the development of hypertriglyceridemia. The increased levels of pre-β HDL subpopulation, which acts as LPL inhibitor, may explain the impact of HDL disturbances on VLDL lipolysis efficiency [69,70]. Additionally, modifications of VLDL and HDL composition and properties influencing their interactions may affect lipolysis; negative correlations were revealed between lipolysis efficiency and apoE and apoCs content in VLDL as well as a positive relationship between lipolysis and HDL-apoC-II and VLDL and HDL apoC-II/apoC-III ratios [69].…”

“…The increased levels of pre-β HDL subpopulation, which acts as LPL inhibitor, may explain the impact of HDL disturbances on VLDL lipolysis efficiency [69,70]. Additionally, modifications of VLDL and HDL composition and properties influencing their interactions may affect lipolysis; negative correlations were revealed between lipolysis efficiency and apoE and apoCs content in VLDL as well as a positive relationship between lipolysis and HDL-apoC-II and VLDL and HDL apoC-II/apoC-III ratios [69]. Moreover,Ćwiklińska et al [69] observed that eGFR-MDRD (The Modification of Diet in Renal Disease Study equation) correlated with the adverse changes in both lipid and apolipoprotein composition of VLDL and HDL.…”

“…Additionally, modifications of VLDL and HDL composition and properties influencing their interactions may affect lipolysis; negative correlations were revealed between lipolysis efficiency and apoE and apoCs content in VLDL as well as a positive relationship between lipolysis and HDL-apoC-II and VLDL and HDL apoC-II/apoC-III ratios [69]. Moreover,Ćwiklińska et al [69] observed that eGFR-MDRD (The Modification of Diet in Renal Disease Study equation) correlated with the adverse changes in both lipid and apolipoprotein composition of VLDL and HDL. For example, despite the reduction of HDL levels with worsening kidney function, the concentration of pre-β1 HDL was increasing with the progression of CKD.…”

Apolipoproteina E şi progresia nefropatiei la pacienţii diabetici

“…La pacienţii HiV pozitiv, homozigozitatea apo ε4 ne arată progresia spre SiDa şi creşterea susceptibilitităţii la infecţii oportuniste. apoe plasmatică apare în principal prin sinteză hepatică; la nivel cerebral, astrocitele produc o cantitate mare de lichid cefalorahidian ce conţine apoe (23,24,25). aSoCIEREa apoE cu unElE afEcţiuni apo ε4 aste asociată cu boala alzheimer familială cu debut tardiv.…”