Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease

Abstract

Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ 2=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease.

The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis

“…Elevated circulating OPG levels have been reported in patients with cardiovascular and/or with chronic renal diseases and it was found to be independently associated with all-cause mortality and atherosclerosis [14, 15]. Similar findings were published in CRF patients on regular HD [40, 41] and in those receiving kidney transplantation [42].…”

MICS, an easily ignored contributor to arterial calcification in CKD patients

“…Matsubara et al (64) found that CKD patients with signs of PEW (defined as subjective global assessment Ͼ 1) or inflammation (CRP Ͼ 10 mg/l) had higher median OPG than controls, which was a predictor of clinical CVD mortality (64). It was reported that increased OPG was positively correlated with IL-6, FGF-23, and high-sensitivity CRP levels in CKD patients (74).…”

Receptor activator of nuclear factor κB ligand/osteoprotegerin axis and vascular calcifications in patients with chronic kidney disease

“…In addition, high OPG levels have been found to correlate with faster progression of aortic calcifications during a 5-year follow-up [21] . Finally, several studies in patients with various CKD stages as well as in renal transplant recipients demonstrated that OPG levels were a significant independent predictor of allcause and cardiovascular mortality during the follow-up period [22][23][24][25][26] . However, one study in ESRD and pre-dialysis CKD patients showed that renal function rather than OPG levels were mostly associated with the progression of aortic and coronary calcifications [27] , whereas another one correlated elevated OPG levels only with moderate CAC [28] .…”