Sabine M Meier1, Anna Wultsch1, Marianne Hollaus1, Markus Ammann1, Elisabeth Pemberger1, Felix Liebscher1, Brigitte Lambers1, Stefanie Fruhwürth1, Tatjana Stojakovic2, Hubert Scharnagl2, Alice Schmidt3, Alexander Springer4, Julia Becker5, Christoph Aufricht5, Ammon Handisurya6, Stefan Kapeller7, Clemens Röhrl1, Herbert Stangl8, Witta Strobl1. 1. Department of Medical Chemistry and Pathobiochemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria. 2. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 3. University Clinic for Internal Medicine III, Medical University of Vienna, Vienna, Austria. 4. Department of Pediatric Surgery, Medical University of Vienna, Vienna, Austria. 5. Department of Pediatrics, Medical University of Vienna, Vienna, Austria. 6. Department of Internal Medicine III, Division of Nephrology & Dialysis, Medical University of Vienna, Vienna, Austria. 7. Institute of Silviculture, University of Natural Resources and Life Sciences, Vienna, Austria. 8. Department of Medical Chemistry and Pathobiochemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria. Electronic address: herbert.stangl@meduniwien.ac.at.
Abstract
AIMS: Patients with chronic kidney disease (CKD) have a high risk to develop atherosclerosis. The capacity of high-density lipoproteins (HDL) or serum to accept cholesterol from macrophages and the capacity of macrophages to export excess cholesterol are critical for the atheroprotective role of reverse cholesterol transport. HDL cholesterol acceptor capacity was reported to be decreased in middle aged hemodialysis patients, but the role of confounding factors remains unclear. MAIN METHODS: We measured the cholesterol acceptor capacity (CAC) of HDL or serum in 12 pediatric and 17 young adult patients with CKD stages 3-5, 14 young adult hemodialysis patients and 15 adult renal transplant recipients without associated diseases and matched controls using THP-1 macrophages. Moreover we studied the cholesterol export capacity (CEC) of patients' monocyte-derived macrophages (HMDMs) to control serum or HDL. KEY FINDINGS: In adults with CKD stages 3-5 serum CAC was slightly increased, whereas CEC of HMDMs was unaltered in both, adult and pediatric patients. In hemodialysis patients, however, serum CAC was markedly reduced to 85±11% of control (p<0.001), presumably due to low serum apolipoprotein A-I. Interestingly, CEC of HMDMs from dialysis patients was increased. In transplant patients no alterations were found. SIGNIFICANCE: CKD without hemodialysis does not reduce cholesterol export from macrophages. Hemodialysis patients might benefit from therapies aiming to restore serum CAC by increasing apolipoprotein A-I. The enhanced export of cholesterol by HMDMs from dialysis patients may represent an adaptive response.
AIMS: Patients with chronic kidney disease (CKD) have a high risk to develop atherosclerosis. The capacity of high-density lipoproteins (HDL) or serum to accept cholesterol from macrophages and the capacity of macrophages to export excess cholesterol are critical for the atheroprotective role of reverse cholesterol transport. HDL cholesterol acceptor capacity was reported to be decreased in middle aged hemodialysis patients, but the role of confounding factors remains unclear. MAIN METHODS: We measured the cholesterol acceptor capacity (CAC) of HDL or serum in 12 pediatric and 17 young adult patients with CKD stages 3-5, 14 young adult hemodialysis patients and 15 adult renal transplant recipients without associated diseases and matched controls using THP-1 macrophages. Moreover we studied the cholesterol export capacity (CEC) of patients' monocyte-derived macrophages (HMDMs) to control serum or HDL. KEY FINDINGS: In adults with CKD stages 3-5 serum CAC was slightly increased, whereas CEC of HMDMs was unaltered in both, adult and pediatric patients. In hemodialysis patients, however, serum CAC was markedly reduced to 85±11% of control (p<0.001), presumably due to low serum apolipoprotein A-I. Interestingly, CEC of HMDMs from dialysis patients was increased. In transplant patients no alterations were found. SIGNIFICANCE: CKD without hemodialysis does not reduce cholesterol export from macrophages. Hemodialysis patients might benefit from therapies aiming to restore serum CAC by increasing apolipoprotein A-I. The enhanced export of cholesterol by HMDMs from dialysis patients may represent an adaptive response.
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