O4
Accelerated progression of vascular calcification in children with CKD is associated with
baseline fetuin-A and vessel characteristics
Rukshana C Shroff 1,2,4, Melanie Hiorns 3, John E Deanfield 2, Cathy Shanahan 4, Lesley Rees 1.
1Renal Unit, Great Ormond Street Hospital for Children, UK 2Vascular Physiology Unit, Institute of
Child Health, London 3Radiology Unit, Great Ormond Street Hospital 4Cardiovascular Division,
King's College London
Background: Vascular calcification is thought to begin early in CKD and progress rapidly on
dialysis. We examined vascular changes as seen on vessel imaging with a quantitative and histological
assessment of the vascular Ca load on arterial biopsy samples to study progression of vascular
changes
through
pre-dialysis
CKD,
dialysis
and
after
transplantation.
Methods: 48 children (16 pre-dialysis CKD 4-5 and 32 on dialysis) had vascular imaging (carotid
intima-media thickness [cIMT], pulse wave velocity [PWV] and coronary artery calcification [CAC]
on CT scan), biomarker analyses and an arterial biopsy (at the time of renal transplantation or PD
catheter insertion). The Ca load in the vessel wall was quantitated and detailed histology performed to
study hydroxyapatite deposition, vascular smooth muscle cell apoptosis and osteogenic
differentiation. 43 children (22 dialysis and 21 transplants) had a second set of imaging after 14.2 ±3.9
months.
Results: The baseline vessel Ca load strongly correlated with cIMT in dialysis patients (p=0.005)
whereas 11 of 16 pre-dialysis patients had normal cIMT. Dialysis patients had a significant annualised
increase in cIMT and PWV (p<0.005 and p=0.03). CAC increased in 5 children with baseline CAC
and was found in 3 others.
cIMT progression showed a close correlation with the vessel Ca load (r=0.59; Figure). Patients with
cIMT progression had the highest apoptotic index implying vascular smooth muscle cell loss and
greater osteogenic differentiation. The baseline cIMT (r=0.31) and Fetuin-A levels (r=0.41), but not
FGF-23, soluble klotho, 25-hydroxyvitamin D or osteopontin associated with cIMT progression.
Changes in PWV and CAC did not correlate with vessel Ca load.
Conclusions: In children on dialysis vascular calcification is rapidly progressive and strongly
correlates with baseline vessel wall characteristics and Fetuin-A levels. No association was found
between vascular measures and FGF-23 or soluble klotho levels.
Relevance: Fetuin-A may be a useful biomarker to predict rapid progression of vascular calcification
in CKD.
Figure - Annualised change in carotid intima media thickness is associated with vessel calcium load.
p = 0.004
R2 = 0.59
Delta change in cIMT
0.25
0.20
0.15
0.10
0.05
0.00
10
25
30
35
40
-0.05
-0.10
Vessel Ca load (g/L)
45
50