Lipoprotein Kinetics in Male Hemodialysis Patients Treated with Atorvastatin

• Published in: Clinical journal of the American Society of Nephrology Vol. 8; no. 8; pp. 1319 - 1326
• Main Authors: Schwaiger, Johannes P, Nakada, Yoshinobu, Berberich, Ramona, Ikewaki, Katsunori, Dieplinger, Benjamin, Zitt, Emanuel, Neyer, Ulrich, Salmhofer, Hermann, Kronenberg, Florian, Koenig, Paul, Dieplinger, Hans
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.08.2013
• Subjects: Adolescent; Adult; Aged; Apolipoproteins B - blood; Atorvastatin Calcium; Cardiovascular Diseases - etiology; Heptanoic Acids - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Kinetics; Lipoproteins - metabolism; Lipoproteins, LDL - blood; Lipoproteins, VLDL - blood; Male; Middle Aged; Original; Pyrroles - pharmacology; Renal Dialysis
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/CJN.10881012

In vivo metabolism of atherogenic apolipoprotein B (apoB)-containing lipoproteins is severely impaired in patients undergoing hemodialysis (HD), resulting in markedly prolonged residence times of these particles. It is unclear whether treatment with statins improves LDL kinetics in HD patients as is known for the general population. Therefore, this kinetic study assessed apoB-containing lipoproteins in these patients. Kinetic measures were analyzed with stable-isotope technology in six men undergoing HD before and after 3 months of daily administration of 10 mg of atorvastatin. Patients were 18-65 years of age, had LDL cholesterol levels between 90 and 200 mg/dl, and had been treated with HD for >6 months. They consumed a standardized isocaloric diet for 3 days before analysis. Fractional catabolic rates (FCRs) and production rates of very-low-density lipoprotein (VLDL)-apoB, intermediate-density lipoprotein-apoB, and LDL-apoB were determined using multicompartment modeling after plasma lipoprotein separation, precipitation of apoB, and determination of tracer-to-tracee ratios using mass spectrometry. Plasma concentrations of VLDL- and LDL-apoB were significantly lower (mean ± SD, 7.77±2.62 versus 11.27±6.15 mg/dl, P<0.05; 56.9±23.9 versus 84.0±21.1 mg/dl, P=0.03) and their FCRs were significantly higher (7.20±3.08 versus 5.20±2.98 days(-1), P<0.05; 0.851±0.772 versus 0.446±0.232 days(-1), P<0.05) after 3 months of atorvastatin treatment. Accordingly, the residence times in plasma of VLDL- and LDL-apoB were significantly lower after treatment (0.14 versus 0.19 day and 1.2 versus 2.2 days, respectively). Lower plasma concentrations and improved kinetics of atherogenic lipoproteins were observed in HD patients after administration of low-dose atorvastatin.