Compositional Lipoprotein Changes and Low-Density Lipoprotein Susceptibility to Oxidation in Chronic Renal Failure Patients with Heavy Proteinuria

Abstract

Background: There are limited data regarding qualitative lipoprotein abnormalities in undialysed uremic patients without proteinuria. In this report, we focused on lipoprotein changes observed in uremic patients with proteinuria as well as on the susceptibility of low-density lipoprotein (LDL) of these patients to oxidative modification in vitro. Methods: 20 patients with chronic renal failure [serum creatinine >1.6 mg/dl (141.4 µmol/l)], but not yet on renal replacement therapy, and with heavy proteinuria (>2 g/24 h), and 18 age- and sex-matched healthy individuals participated in the study. In both patients and controls, venous blood was collected for determination of serum lipid and lipoprotein levels, lipoprotein subfraction profile and chemical composition, as well as the susceptibility of LDL subfractions to oxidation. Results: Patients exhibited a more atherogenic lipid profile compared with the control population. Furthermore, the total very LDL + intermediate-density lipoprotein mass was increased in patients compared with controls, while this subfraction was triglyceride enriched in uremic patients. The total LDL concentration was significantly higher in patients compared with controls due mainly to an increase in the mass of all lipoprotein subfractions. It is noteworthy that the mass of small dense LDL was significantly elevated in patients compared with controls (135 ± 12 vs. 115 ± 11 mg/dl, p = 0.01), an increase which was more pronounced in hypertriglyceridemic patients. Furthermore, the subfraction high-density lipoprotein-2 mass was significantly lower in uremic patients compared with controls. Finally, no significant differences in the lag time, the rate of oxidation and the relative electrophoretic mobility values in each LDL subfraction between the two groups were observed. Conclusion: We conclude that uremic patients with heavy proteinuria exhibit compositional lipoprotein changes that are less marked than those observed in nonuremic patients with nephrotic syndrome. However, there is no evidence that circulating LDL isolated from these patients is more susceptible to oxidation in vitro than lipoprotein isolated from age- and gender-matched controls.

Proteinuria converts hepatic heparan sulfate to an effective proprotein convertase subtilisin kexin type 9 enzyme binding partner

“…We did not investigate the possible effects of proteinuria on lipoprotein composition (for instance, oxidation of LDLc). 67 Therefore, its eventual effects on receptor binding need to be investigated in future studies.…”

Lipid Abnormalities and Cardiovascular Risk in Renal Disease

“…Mainly as a result of decreased catabolism 3 of chylomicrons 4 and endogenous lipoprotein particles, 5 remnants of chylomicron and very-low-density lipoprotein 4 as well as LDL 6 accumulate, and in parallel so does small dense LDL. 7,8 Another typical disturbance is post-translational modification of apolipoproteins, 9 particularly apolipoprotein B100 by glycation, 10 oxidation, 11 and carbamylation. 12 Such modifications of lipids 13 interfere with uptake of LDL by the classical LDL receptor, favoring uptake by the scavenger receptor LOX1, which plays an important role in atherogenesis.…”