Osteoprotegerin Is a Better Predictor for Cardiovascular and All-Cause Mortality than Vascular Calcifications in a Multicenter Cohort of Patients on Peritoneal Dialysis

Abstract

The purpose of this study was to compare vascular calcification (VC), serum osteoprotegerin (OPG) levels, and other biochemical markers to determine their value as available predictors of all-cause and cardiovascular (CV) mortality in patients on peritoneal dialysis (PD). A total of 197 patients were recruited from seven dialysis centers in Mexico City. VC was assessed with multi-slice computed tomography and a calcification score(CaSc) was generado. OPG, albumin, calcium, hC-reactive protein, phosphorous, osteocalcin, total alkaline phosphatase, and intact parathormone were also analyzed. Follow-up and mortality analyses were assessed using the Cox regression model. The mean age was 43.9 ± 12.9 years, 64% were males, and 53% were diabetics. The median OPG was 11.28 (IQR: 7.6–17.4 pmol/L), and 42% of cases had cardiovascular calcifications. The median VC was 424 (IQR:101–886). During follow-up (23 ± 7 months), there were 34 deaths, and 44% were cardiovascular in origin. In multivariable analysis, OPG was a significant predictor for all-cause (HR 1.08; p < 0.002) and CV mortality (HR 1.09; p < 0.013), and performed better than VC (HR 1.00; p < 0.62 for all-cause mortality and HR 1.00; p < 0.16 for CV mortality). For each mg/dL of albumin-corrected calcium, there was an increased risk for CV mortality, and each g/dL of albumin decreased the risk factor for all-cause mortality. OPG levels above 14.37 and 13.57 pmol/L showed the highest predictive value for all-cause and CV mortality in incident PD patients and performed better than VC.

Vascular calcification inhibitors and cardiovascular events in peritoneal dialysis patients

“…This contrast could be explained by the stimulation of OPG synthesis by cytokines, which emerge due to chronic inflammation and excess volume. So, contrary to expectations, VC and mortality may have been found higher in groups with high OPG levels [47,51,53,55,56,65,67].…”

“…In this context, the positive correlation between high OPG levels and VC is quite surprising [58]. High OPG levels are also correlated with CVDs, including cerebrovascular diseases, peripheral arterial diseases, heart valve diseases, and coronary artery diseases where VC and inflammation are risk factors [51]. The contradiction here results from the differences between observations in humans and other experimental research [51,58].…”

“…OPG is a glycoprotein and a member of the TNF receptor family. It is synthesized from numerous tissues and cells, particularly osteoblasts, hematopoietic cells, immune cells, and vascular bed cells [51]. The synthesis of OPG is stimulated by inflammatory cytokines, mainly IL-1 and TGF-α/β.…”

“…The fact that OPG is synthesized by vascular endothelial and smooth muscle cells has suggested that it could play a role in the structure and functions of the vascular bed [57]. It inhibits apoptosis and enables endothelial cells to maintain their vitality [51,57]. Evidence has shown the absence of OPG to cause great vessel calcification, media and intima proliferation, and aortic dissection, which suggests that OPG protects the great vessels against calcification [52].…”

“…High OPG levels are also correlated with CVDs, including cerebrovascular diseases, peripheral arterial diseases, heart valve diseases, and coronary artery diseases where VC and inflammation are risk factors [51]. The contradiction here results from the differences between observations in humans and other experimental research [51,58]. Numerous research on HD patients found a correlation between high OPG levels and aortic calcification, coronary artery calcification, and mortality [58,59].…”