title: The impact of chronic kidney disease and short-term treatment with rosiglitazone on plasma cell-free DNA levels.
abstract: Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. Circulating free nucleic acids, known as cell-free DNA (cfDNA), have been proposed as a novel biomarker of cardiovascular risk. The impact of renal impairment on cfDNA levels and whether cfDNA is associated with endothelial dysfunction and inflammation in CKD has not been systematically studied. We analysed cfDNA concentrations from patients with varying degrees of CKD. In addition, to determine whether there is a relationship between cfDNA, inflammation, and endothelial dysfunction in CKD, levels of proinflammatory cytokines and von Willebrand Factor (vWF) were measured in patients treated with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone or placebo for 8 weeks. cfDNA levels were not increased with renal impairment or associated with the degree of renal dysfunction (P = 0.5). Treatment with rosiglitazone for 8 weeks, but not placebo, was more likely to lead to a reduction in cfDNA levels (P = 0.046); however, the absolute changes in cfDNA concentrations during treatment were not statistically significant (P > 0.05). cfDNA levels correlated with markers of endothelial dysfunction (hsCRP P = 0.0497) and vWF (P = 0.0005). In conclusion, cell-free DNA levels are not influenced by renal impairment but do reflect endothelial dysfunction in patients with CKD.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia ; Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia.
authors.forename: Amanda L
authors.identifier: 0000-0002-1261-9236
authors.initials: AL
authors.lastname: McGuire
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, WA, Australia.
authors.forename: Nadia
authors.identifier: 0000-0002-2081-1172
authors.initials: N
authors.lastname: Urosevic
authors.affiliation: Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
authors.forename: Doris T
authors.initials: DT
authors.lastname: Chan
authors.affiliation: Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
authors.forename: Gursharan
authors.initials: G
authors.lastname: Dogra
authors.affiliation: Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, WA, Australia ; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia.
authors.forename: Timothy J J
authors.initials: TJ
authors.lastname: Inglis
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia ; Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia ; Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia ; Translational Renal Research Group, Harry Perkins Institute of Medical Research, 5th Floor QQ Block, QEII Medical Centre, 6 Verdun Street, Nedlands 6009, Australia.
authors.forename: Aron
authors.identifier: 0000-0003-3369-4187
authors.initials: A
authors.lastname: Chakera