Elevated serum osteoprotegerin levels are associated with inflammation, malnutrition, and new onset cardiovascular events in peritoneal dialysis patients

Abstract

Backgrounds : Osteoprotegerin (OPG) is known to regulate bone mineral metabolism and to be also associated with inflammation, cardiovascular disease (CVD), and mortality. Malnutrition–inflammation-atherosclerosis (MIA) syndrome is commonly found and closely linked to mortality in patients with renal failure. The aim of this study was to investigate the associations between OPG and MIA syndrome in prevalent peritoneal dialysis (PD) patients. Methods : Prevalent PD patients for more than 6 months were followed from March 2005 to May 2010. At baseline, OPG, hs-CRP, albumin, and % lean body mass (LBM) by creatinine kinetics were checked, and subjective global assessment (SGA) was performed. New-onset cardiovascular events and patient’s mortality were evaluated during the study period. Based on the median level of OPG, patients were classified as lower OPG (LO) group (n = 88) and higher OPG (HO) group (n = 88).Results : A total of 176 patients (age 52.0 ± 11.8 years, male 50.6%, duration of PD 105.3 ± 67.2 months) were recruited and followed. In HO group, age, hs-CRP levels, and Charlson’s comorbidity indices were higher, while serum albumin levels, %LBM, and SGA score were significantly lower than LO group. OPG levels were positively correlated with inflammatory markers, whereas negatively correlated with nutritional status. Cardiovascular events occurred in 51 patients during the study period. Univariate cox regression analysis revealed OPG to be a risk factor for newly developed CVD [per an increase by 1 in log OPG, Hazard ratio (HR): 2.34; 95% Confidence interval (CI): 1.35~4.04; p = 0.002], which remained significant after adjustment for age, sex, diabetes, and duration of PD. (HR: 2.00; 95% CI: 1.13~3.89; p = 0.02). However when hs-CRP levels and %LBM were included for further adjustment, the significance of OPG disappeared (HR: 1.92; 95% CI: 0.96~3.63; p = 0.06, HR: 1.79; 95% CI: 0.92~3.53; p = 0.09 respectively). A total of 28 patients died. Mortality rate was higher in HO group than in LO group (n = 20, 22.7% versus n = 8, 9.1%), but there was no statistical significance (p = 0.06).Conclusion: Serum OPG levels were significantly correlated with markers of systemic inflammation and malnutrition. Also, OPG worked as a significant predictor of newly developed CVD in PD patients. These findings suggest OPG might be a prognostic indicator of MIA syndrome in prevalent PD patients.