Abstract
Abstract Background and Aims Osteoprotegerin (OPG), which is an osteoclastic inhibitory factor, have been shown associated with adverse renal outcomes and progression of vascular calcification in chronic kidney disease (CKD) patients. Anemia and CKD-bone mineral disorders (CKD-MBD) are also frequently observed in these patients. Since CKD-MBD and anemia might be closely linked, therefore, we further examined whether OPG level as a marker for bone turnover can predict the future development of anemia in a large-scale prospective cohort. Method Among 2,238 patients with non-dialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD), 2,086 patients who measured hemoglobin, hepcidin, iron profiles and OPG level were included in the analysis. Anemia was defined as a hemoglobin level of < 13.0 g/dL and 12.0 g/dL for male and female, respectively. Results The mean age was 53.6 ± 12.2 years and 1,270 (60.9%) patients were males. At baseline, anemia was found in 941 (45.1%) patients. Log transformed OPG levels significantly correlated with FGF23 levels, but inversely with iron profiles and hemoglobin levels at baseline. A multivariate logistic regression model showed that log OPG level was independently associated with the prevalence of anemia (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.41-3.48, P=0.001). Among 1110 patients without baseline anemia, 258 (25.3%) patients developed anemia during a median follow-up duration of 34.6 (interquartile range, 23-48) months. In the fully adjusted multivariable Cox models, risk of developing anemia was significantly higher in the fourth (hazard ratio [HR], 1.99; 95% CI, 1.08-3.67; P =0.028) than in the first OPG quartile. Similar association was observed in a model when OPG was treated as a continuous variable. Conclusion We showed that high serum OPG levels are associated with an increased risk of developing anemia in patients with non-dialysis CKD.
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