title: Restoration of renal function does not correct impairment of uremic HDL properties.
abstract: Cardiovascular disease remains the leading cause of death in renal transplant recipients, but the underlying causative mechanisms for this important problem remain elusive. Recent work has indicated that qualitative alterations of HDL affect its functional and compositional properties in ESRD. Here, we systematically analyzed HDL from stable renal transplant recipients, according to graft function, and from patients with ESRD to determine whether structural and functional properties of HDL remain dysfunctional after renal transplantation. Cholesterol acceptor capacity and antioxidative activity, representing two key cardioprotective mechanisms of HDL, were profoundly suppressed in kidney transplant recipients independent of graft function and were comparable with levels in patients with ESRD. Using a mass spectroscopy approach, we identified specific remodeling of transplant HDL with highly enriched proteins, including α-1 microglobulin/bikunin precursor, pigment epithelium-derived factor, surfactant protein B, and serum amyloid A. In conclusion, this study demonstrates that HDL from kidney recipients is uniquely altered at the molecular and functional levels, indicating a direct pathologic role of HDL that could contribute to the substantial cardiovascular risk in the transplant population.
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Chantal
authors: C
authors: Kopecky
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Michael
authors: M
authors: Haidinger
authors: Institute of Pathology, Center of Medical Research, Omics Center Graz, and.
authors: Ruth
authors: R
authors: Birner-Grünberger
authors: Austrian Center of Industrial Biotechnology, Graz, Austria.
authors: Barbara
authors: B
authors: Darnhofer
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Christopher C
authors: CC
authors: Kaltenecker
authors: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria; and.
authors: Gunther
authors: G
authors: Marsche
authors: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria; and.
authors: Michael
authors: M
authors: Holzer
authors: Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria;
authors: Thomas
authors: T
authors: Weichhart
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Marlies
authors: M
authors: Antlanger
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Johannes J
authors: JJ
authors: Kovarik
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Johannes
authors: J
authors: Werzowa
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
authors: Manfred
authors: M
authors: Hecking
authors: Division of Nephrology and Dialysis, Department of Internal Medicine III, and marcus.saemann@meduniwien.ac.at.
authors: Marcus D
authors: MD
authors: Säemann
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000737:chemistry*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D014511:Uremia / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL
keywords: CKD; cardiovascular disease; dyslipidemia; lipids; renal transplantation