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J Am Soc Nephrol. 2015 Mar;26(3):565-75. doi: 10.1681/ASN.2013111219. Epub 2014 Jul 28.

Restoration of renal function does not correct impairment of uremic HDL properties.

Author information

1
Division of Nephrology and Dialysis, Department of Internal Medicine III, and.
2
Institute of Pathology, Center of Medical Research, Omics Center Graz, and.
3
Austrian Center of Industrial Biotechnology, Graz, Austria.
4
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria; and.
5
Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria;
6
Division of Nephrology and Dialysis, Department of Internal Medicine III, and marcus.saemann@meduniwien.ac.at.

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.

KEYWORDS:

CKD; cardiovascular disease; dyslipidemia; lipids; renal transplantation

PMID:
25071090
PMCID:
PMC4341473
DOI:
10.1681/ASN.2013111219
[Indexed for MEDLINE]
Free PMC Article
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