Osteoprotegerin Is the Strongest Predictor for Progression of Arterial Calcification in Peritoneal Dialysis Patients

Abstract

Background: Arterial calcification (AC) is frequent in patients with end stage renal disease and is also considered a risk factor for later morbidity and mortality. However, long-term factors associated with the process are not well known. We analyzed the trends over time of biomarkers related with development and progression of AC in incident patients on peritoneal dialysis (PD). Methods: We performed a prospective study with 186 patients on PD followed up for 1 year. We analyzed the progression of AC in the abdominal aorta and pelvic vessels by calcification score (CaSc), using16-cut computerized multidetector tomography at baseline and 1 year. Variables related with PD treatment, inflammation, and mineral metabolism were measured at baseline, 6, and 12 months of follow-up. Changes in biochemical variables were analyzed for their relationship with changes in AC. Results: Over 1 year, the number of patients with AC increased from 47 to 56%, and CaSc from 355 (interquartile range [IQR] 75-792) to 529 (IQR 185-1632). A total of 43.5% of patients remained free of calcification, 11.7% had new calcifications, and 44.8% had progression of calcification. Older age, diabetes, high systolic blood pressure, body mass index, cholesterol, and osteoprotegerin (OPG), as well as lower levels of albumin, serum creatinine, and osteocalcin, were associated with development of new, and rapid progression of, calcification. In multivariate logistic analysis, OPG remained the most significant (OR 1.27, 95% CI 1.11-1.47, p < 0.001). Conclusion: OPG was the strongest risk factor associated with new development and rapidprogression of AC in incident PD patients.

Coronary Artery Calcification in Hemodialysis and Peritoneal Dialysis

“…First, we found that osteoprotegerin was associated with progression of CAC, in accordance with previous studies [28,29]. Nevertheless, osteoprotegerin should theoretically protect against vascular calcification by preventing the receptor activator of nuclear factor-κB ligand from binding to the RANK receptor [30].…”

Serum osteoprotegerin level is positively associated with peripheral artery disease in patients with peritoneal dialysis

“…In patients with PAD, the serum OPG level was inversely correlated with ABI and positively correlated with severity grade of PAD, which could be modulated by inflammation [25]. When considering PAD, serum OPG levels were similar to old age, DM, HTN, hypoalbuminemia, or low creatinine level, which were considered as possible risk factors in patients on PD or renal transplantation [12,13]. Consistent with these studies, we found that OPG remained a significant predictor of PAD development with 1.027-fold increased risk in PD patients.…”

“…Evidence had shown that patients on HD had non-significant higher levels of OPG than those on PD but patients on both modalities had higher levels than CKD or control patients and the OPG level was significantly correlated with inflammatory markers, such as interleukin-6, albumin, and CRP [10,11]. Moreover, Avila et al showed that OPG was associated with more severe arterial calcification in PD patients [13]. Studies had shown that OPG levels could be modulated by inflammatory cytokines, and the presence and severity of PAD were correlated with inflammation [10,11,17,20].…”

“…In patients with chronic kidney disease (CKD), the serum OPG level progressively elevates as the renal function deteriorates, positively correlates with inflammatory markers and intimal-media thickness of carotid arteries, and is most importantly associated with survival [10,11]. In addition, the OPG level was significantly correlated with PAD after renal transplantation [12] and was considered as the strongest predictor of arterial calcification progression in patients on PD [13]. Having PAD was a predictor for further CV morbidity and mortality in the general population, patients with DM, and even those with CKD; however, studies regarding the relationship between the serum OPG level and PAD measured using ABI in patients on PD remained limited.…”

Aortic Arch Calcification and Bone-Associated Molecules in Peritoneal Dialysis Patients

“…Previous studies suggest that OPG is an arterial calcification inhibitor and is released by endothelial cells as a protective mechanism to ensure their survival in certain pathological conditions, such as diabetes mellitus, chronic kidney disease, and other metabolic disorders [21][22][23][24]. Higher OPG levels have been independently associated with cardiovascular events in PD patients [25] and have been positively correlated with the area of the aorta affected by VC, as assessed by CT [26]. It is therefore possible that OPG is a novel biomarker of CVD in PD patients [27].…”