Elevated osteoprotegerin is associated with all-cause mortality in CKD stage 4 and 5 patients in addition to vascular calcification.
BACKGROUND
Cardiovascular disease is the leading cause of death in the chronic kidney disease (CKD) population. The mechanisms of vascular damage are not fully understood. The objective of this study was to prospectively investigate the importance of novel mediators of vascular damage, in conjunction with vascular calcification (VC), on survival.


METHODS
A total of 134 subjects [60 haemodialysis (HD), 28 peritoneal dialysis (PD) and 46 CKD stage 4] were studied. All survivors completed 40 months of follow-up. VC was measured using multi-slice spiral CT of the superficial femoral artery. Circulating osteoprotegerin (OPG), Fetuin-A and high sensitivity C-reactive protein (hs-CRP) were measured in addition to standard clinical biochemical analysis.


RESULTS
After a 40-month follow-up, 31 patients had died (27 men and 4 women). Of 31 subjects, 31 had evidence of significant VC. The majority of deaths were in the HD group (48%), 36% were PD subjects and 16% were CKD subjects. The outcome of interest was survival at the end of follow-up. Multivariate logistical regression analysis revealed male gender [OR 8.06 (1.34-48.450) P = 0.02], OPG >25 pmol/L [OR 5.31(1.35-20.88) P = 0.02] and hypoalbuminaemia [OR 0.26 (0.12-0.56) P < 0.01], were associated with increased odds of death.


CONCLUSIONS
We have previously reported that VC and low albumin predict death in CKD stages 4 and 5 over a 2-year follow-up period. These data show that OPG, independent of CRP, is also associated with a negative outcome. The mechanisms remain to be elucidated; however, it is likely that they are associated with vascular damage through mechanisms in addition to VC.
Sigrist
Mhairi K
MK
School of Graduate Entry Medicine and Health, The University of Nottingham, Derby, UK. msigrist@providencehealth.bc.ca
Levin
Adeera
A
Er
Lee
L
McIntyre
Chris W
CW
D002097:C-Reactive Protein / Q000032:analysis; D002114:Calcinosis / Q000097:blood* / Q000209:etiology*; D002423:Cause of Death; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000145:classification / Q000150:complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011446:Prospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D014652:Vascular Diseases / Q000097:blood* / Q000209:etiology*
D053244:Osteoprotegerin; D002097:C-Reactive Protein