P149
ABNORMALITIES OF THE OPG/RANKL AXIS IN PROGRESSIVE KIDNEY
FAILURE: THE VARIABLE INFLUENCE OF DIABETES
Singh, D, Winocour, P, Summerhayes, B, Viljoen, A, Sivakumar, G, Farrington, K
East and North Herts NHS Trust, Lister Hospital, Stevenage
The high prevalence of cardiovascular disease and vascular calcification in chronic kidney
disease (CKD) is associated with both traditional and uremic-specific risk factors. These include
hyperphosphatemia, high calcium x phosphate product, chronic inflammation, dyslipidemia and
other dialysis-related factors. Recently the role of osteoprotegerin (OPG) and receptor activator
of nuclear factor kappa--ligand (RANKL) in bone and vascular adaptations has become
apparent. This study was designed to investigate the influence of kidney failure on this axis in
diabetic and non diabetic subjects.
Seventy patients were studied – 20 with Stage 3 CKD (CKDMod), 20 with Stage 4 and 5 CKD
(CKDAdv) and 30 on Haemodialysis (CKDHD). Each groups had equal number of diabetics and
non-diabetics. Serum OPG and RANKL were measured along with parameters reflecting renal
function and mineral metabolism.
Serum calcium was higher in the CKDHD group than in the CKDMod (2.43 mmol/l vs 2.38
mmol/l: p = 0.026). Median PTH levels were higher in the CKDHD group than in the CKDAdv (p
< 0.001) and the CKDMod group (p < 0.001) (19.1 vs.5.5 vs 3.2 pmol/l respectively). OPG levels
correlated significantly with serum calcium (r = 0. 289: p = 0.015) and PTH levels (r = 0.439: p
< 0.001).
Mean OPG levels in the CKDHD group were higher than in the CKDAdv group (p< 0.001) and the
CKDMod group (p<0.001) (9.8 vs. 5.8 vs 5.4 respectively). There were no differences in RANKL
levels across the groups. The OPG/RANKL ratio was significantly different across the groups
(p = 0.038). Median OPG/RANKL ratio was higher in the CKDHD group than in the CKDAdv
group (p = 0.016) and the CKDMod group (p = 0.066) (109 vs. 45: vs. 61 respectively).
In the CKDMod group OPG levels were higher in diabetic patients than in non-diabetics (6.1 vs.
4.5 pmol/l: p = 0.032). The same was true in the CKDAdv group (6.7 vs. 4.6 pmol/l: p = 0.032).
However, in the CKDHD group, diabetics had lower OPG levels (8.6 vs. 10.9 pmol/l), though
this difference did not reach statistical significant (p = 0.079).
OPG is secreted by endothelial cells and tends to protect against VC. Rising OPG levels in
progressive kidney failure imply mobilisation of protective adaptations to the increased calcific
stimulus generated by falling kidney function. The higher OPG levels in diabetics in moderate
to advanced CKD can be similarly interpreted. The reversed ratio in HD patients suggests
relative failure of protective mechanisms in diabetics in this setting, resulting in an increased
calcification potential.