Unique features of the pathophysiology of dyslipidemia in CKD

What are the Unique features of the pathophysiology of dyslipidemia in CKD?

A number of unique clinical features among patients with CKD and those on dialysis lead to changes in the structure and function of lipid molecules.

Uremia and frequent heparinization in dialysis patients can decrease the activity of lipoprotein lipase and hepatic triglyceride lipase necessary to cleave triglycerides into free fatty acids. Incomplete triglyceride catabolism causes an accumulation of remnant particles (chylomicrons) that contribute to increased atherosclerosis.

Although the concentration of LDL cholesterol is often no higher than that in the general population, there are differences in the qualitative nature of LDL cholesterol.

Small dense LDL (sdLDL) and intermediate LDL (ILDL) fractions are increased in CKD. The decreased activity of lipases described above prevents the degradation of very-low-density LDL (VLDL) into LDL cholesterol, resulting in the accumulation of ILDL.

The increased plasma residence time of these particles further results in structural changes in the apo(B) protein they carry, decreasing hepatic clearance.

Decreased clearance by the liver results in uptake by macrophages, which may result in adherence to the vascular endothelium, leading to plaque formation.

CKD is also associated with change in the distribution of HDL cholesterol fractions. Low apo-AI level and decreased lecithin:cholesterol acyltransferase (LCAT) activity result in reduced esterification of free cholesterol and a reduced cholesterol-carrying capacity of HDL molecules.

Proteinuric kidney diseases, especially nephrotic syndrome, are characterized by elevations in plasma Lp(a) concentrations, LDL, and total cholesterol due to increased liver production. In addition, there is a reduction in the cardioprotective HDL2 component of HDL cholesterol.

Proteinuria also leads to an elevated free fatty acid to albumin ratio. Angiopoietin-like 4 (angptl4) is a protein expressed primarily in the liver, and its levels are elevated in nephrotic syndrome in response to these free fatty acids.

Angptl4 inhibits lipoprotein lipase, leading to hypertriglyceridemia in persons with nephrotic syndrome.

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