O96
High-density lipoprotein in children with chronic kidney disease promotes endothelial dysfunction and
early atherosclerosis
Rukshana Shroff 1,2*; Thimoteus Speer 3*; Sophie Colin 4; Marietta Charakida 2; Bart Staels 4; Danilo Fliser
3; Ulf Landmesser 5; John E Deanfield 2
1 Nephrology Unit, Great Ormond Street Hospital for Children and University College London Institute of
Child Health, London, UK 2 Vascular Physiology Unit, University College London Institute of Child Health,
London, UK 3 Saarland University Medical Centre, Department of Internal Medicine, Nephrology and
Hypertension, Homburg/Saar, Germany 4 Université Lille 2; Inserm, U1011; EGID; Institut Pasteur de Lille,
Lille, France 5 University Hospital Zurich, Cardiovascular Center, Zurich, Switzerland
Introduction Endothelial dysfunction begins in early chronic kidney disease and contributes to
cardiovascular mortality. High-density lipoprotein (HDL) is considered anti-atherogenic, but may have
adverse vascular effects in patients with cardiovascular disease, diabetes and inflammatory conditions. The
effect of renal failure per se on HDL properties is not known.
Methods We studied the endothelial effects of HDL in 82 children with CKD stages 2 - 5, dialysis and
transplant (HDLCKD) who were free of underlying inflammatory diseases (confirmed on arterial biopsies),
diabetes or active infections.
Results Compared to HDL from healthy children, HDLCKD strongly inhibited endothelial nitric oxide
production (Figure 1), promoted endothelial superoxide production, increased vascular cell adhesion
molecule-1 expression and reduced cholesterol efflux from macrophages. Endothelial effects of HDL were
abnormal even in CKD stage 2, with most profound changes in dialysis, and partial recovery after kidney
transplantation. HDLCKD was associated with increased aortic pulse wave velocity, carotid intima-media
thickness and circulating markers of endothelial dysfunction (urate, angiopoietin-2 and IL-6). Symmetric
dimethylarginine levels were increased in serum and in the fractions of HDLCKD.
In a longitudinal follow-up of 8 children before and 3-months after kidney transplantation, HDL induced nitric
oxide, superoxide and VCAM-1 production significantly improved after transplantation but did not reach
normal levels.
Figure 1. - HDL from CKD patients reduces endothelial nitric oxide production
Conclusions In children with CKD, and without concomitant disease affecting HDL function, HDL exerted a
range of adverse vascular effects that were associated with clinical markers of endothelial dysfunction and an
abnormal vascular phenotype. These changes closely correlated with the level of renal dysfunction and
showed partial improvement after kidney transplantation.