P143 (RA6321)
Affect of IL-6 Genotype on Intact PTH Levels in Stable Haemodialysis Patients
T Pile1, M Varagunam2, A Chesser1, N Ashman1, MJ Raftery2 and MM Yaqoob1
1
Department of Nephrology, Barts and the London NHS Trust, Whitechapel, Renal
Unit, Royal London Hospital, Whitechapel, London, E1 1BB, United Kingdom and
2
Experimental Medicine and Nephrology, St. Bartholomews and the Royal London
Medical School, London, United Kingdom
Renal osteodystrophy is a debilitating complication of uraemia. The severity of this
complication varies significantly among individual patient populations. Apart from
calcium and phosphate dysregulation, several local factors in the bone, such as IL-6,
play a significant role in bone remodelling both in health and in disease. Higher Il-6
levels are associated with osteopenia in post-menopausal women. Moreover IL-6
production by the osteoblast in response to parathyroid hormone (PTH) acts via it’s
receptor on osteoclasts resulting in bone resorption. Systemic levels of IL-6 are
genetically determined by a single nucleotide polymorphism in the promoter sequence
of the IL-6 at the -174 G>C gene. The functional role of IL-6 in uraemic patients and
in renal bone disease is not known. In health the IL-6 GG genotype is associated with
an overproduction in IL-6 . But in diseased states such as uraemia the C-allele
becomes the overproducer.
We hypothesise that IL-6 genotype plays a functional role in determining intact PTH
(iPTH) levels in a homogenous haemodialysis (HD) population. In order to avoid the
confounding factors of race and dialysis modality, we studied 62 stable white HD
patients (41.9 % male, 17.8% diabetic) from a cohort of 209 patients on the transplant
waiting list. The groups were divided into those containing the CC or CG genotype
(n= 37) and those containing the GG genotype (n= 25). A time averaged iPTH over 1
year was determined. The iPTH was analysed in relation to -174 IL-6 promoter
genotype (CC-CG vs GG), age, duration on dialysis, dose of calcium supplementation
(gm/day), dose of alphacalcidol supplementation (mcg/day) and serum calcium,
phosphate, alkaline phosphatase and CRP levels.
The mean PTH was not significantly different between the two groups (CC-CG 35.43
± 8.057, GG 39.61± 7.9, p= 0.914). On multivariate analysis the following were
significant variables: age, serum Alkaline Phosphatase and serum phosphate level (p=
0.05, 0.02 and 0.006 respectively). We were unable to show a link between IL-6
genotype and PTH levels. There was no relation between duration on dialysis, serum
calcium or CRP, calcium and alphacalcidol supplementation, kt/v and PTH levels.
We conclude that despite evidence of the local interaction of PTH and IL-6 at the
tissue level of the bone no such relationship exists at the systemic level between these
two bone tropic factors.