Association of Dyslipidemia, Oxidative Stress, and Inflammation With Redox Status in VLDL, LDL, and HDL Lipoproteins in Patients With Renal Disease

Abstract

Some cardiovascular complications in patients with chronic kidney disease and end-stage renal disease may be caused by structurally and functionally modified lipoproteins. Redox status (advanced oxidation protein products [AOPPs]), prooxidant-antioxidant balance, total protein sulfhydryl (SH-groups), and paraoxonase 1 (PON1) activity were assessed in 77 renal patients and 20 controls. Lipoproteins were isolated using ultracentrifugation. PON1, PON3, and pentraxin-3 concentration were determined by enzyme-linked immunosorbent assay (ELISA). Dyslipidemia-Oxy-Inflammation (DOI) score was calculated as a sum of dyslipidemia, oxidative stress, and inflammation scores. The dyslipidemia score ( P < .001), oxy score ( P < .01), inflammation score (P < .001), and the DOI score ( P < .001) were higher in patient groups compared with controls. The very-low-density lipoprotein (VLDL) fraction contained the highest amount of AOPP ( P < .001) compared with other lipoprotein fractions in all groups. The low-density lipoprotein (LDL) fraction contained elevated AOPP in all groups compared with the high-density lipoprotein (HDL) fraction ( P < .001). Significant positive correlation was observed between AOPP in LDL fraction and DOI score (ρ = 0.510, P < .01). Dyslipidemia, oxidative stress, and inflammation play an interactive role in renal disease and are mutually associated with redox status in VLDL, LDL, and HDL lipoproteins in plasma of renal patients.

Paraoxonase 1 and atherosclerosis‐related diseases

“…In addition to PON1 activity, significantly decreased PON1 in serum was found in renal patients . This result was also confirmed in our study in isolated HDL lipoprotein fractions and suggested reduced antioxidant potential of HDL particles in renal disease . Given that free SH‐groups have the potential to neutralize oxidized phospholipids and cholesterol esters, decreased PON1 in serum, as well as in isolated HDL lipoprotein fractions may lead to oxidative damage of other lipoproteins, including HDL particles .…”

“…In addition, increased uremic toxins could be an additional reason for decreased PON1 concentration in renal patients due to interference with the synthesis of PON1 itself . Furthermore, our recent study revealed significantly reduced PON3 in patients with chronic kidney disease, as well as in patients on hemodialysis . A limited number of studies analyzed PON3 in renal pathology.…”

“…90 This result was also confirmed in our study in isolated HDL lipoprotein fractions and suggested reduced antioxidant potential of HDL particles in renal disease. 91 Given that free SH-groups have the potential to neutralize oxidized phospholipids and cholesterol esters, decreased PON1 in serum, as well as in isolated HDL lipoprotein fractions may lead to oxidative damage of other lipoproteins, including HDL particles. 91,92 In addition, increased uremic toxins could be an additional reason for decreased PON1 concentration in renal patients due to interference with the synthesis of PON1 itself.…”

“…91 Given that free SH-groups have the potential to neutralize oxidized phospholipids and cholesterol esters, decreased PON1 in serum, as well as in isolated HDL lipoprotein fractions may lead to oxidative damage of other lipoproteins, including HDL particles. 91,92 In addition, increased uremic toxins could be an additional reason for decreased PON1 concentration in renal patients due to interference with the synthesis of PON1 itself. 83 Furthermore, our recent study revealed significantly reduced PON3 in patients with chronic kidney disease, as well as in patients on hemodialysis.…”

“…83 Furthermore, our recent study revealed significantly reduced PON3 in patients with chronic kidney disease, as well as in patients on hemodialysis. 91 A limited number of studies analyzed PON3 in renal pathology. One that did showed that in an animal model the absence of PON3 led to elevated inflammation, oxidative stress, and, consequently, increased progression of atherosclerosis.…”