Biomarkers of mineral and bone metabolism and 20-year risk of hospitalization with infection: The atherosclerosis risk in communities study

Context: Mineral and bone disorders (MBDs) might be relevant in the etiology of infection. Objective: To determine whether MBD biomarkers were associated with the incidence of hospitalization with infection. We also assessed the cross-sectional association between MBD biomarker levels and kidney function. Design, Setting, Participants: Community-based cohort study of 11,218 participants with an estimated glomerular filtration rate (eGFR) $30 mL/min/1.73m2 in the Atherosclerosis Risk in Communities study. We assessed the cross-sectional associations of five MBD markersfibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium corrected for hypoalbuminemia, and phosphoruswith eGFR from 1990 to 1992 and their longitudinal associations with incident hospitalization with infection in 1990 to 2013. Main Outcome: Incident hospitalization with infection. Results: In age-, sex-, and race-adjusted models, lower eGFRs were significantly associated with greater levels of FGF23, PTH, and corrected calcium but not 25(OH)D or phosphorus. During followup, 5078 hospitalizations with infection occurred. In fully adjusted Cox models, with the second quartile as the reference, the hazard ratio (HR) was significantly greater in the highest quartile of FGF23 [HR, 1.12; 95% confidence interval (CI), 1.03 to 1.21], PTH (HR, 1.09; 95% CI, 1.01 to 1.18), and corrected calcium (HR, 1.11; 95% CI, 1.03 to 1.20), and lowest quartile for 25(OH)D (HR, 1.11; 95% CI, 1.03 to 1.21). The association with phosphorus was significant only when the outcome was restricted to primary diagnosis of infection. These findings were consistent across subgroups of age, sex, race, and eGFR (,60 vs $60 mL/min/1.73 m2). Conclusions: MBD biomarkers were associated with eGFR and the subsequent risk of infection, supporting MBD involvement in the etiology of infection.