Serum alkaline phosphatase and mortality in hemodialysis patients

BACKGROUND: Alkaline phosphatase is typically considered as an innocent by-stander, but emerging data suggest that alkaline phosphatase might play a pathogenic role in vascular calcification and thus contribute to increased mortality in hemodialysis patients. STUDY DESIGN: Longitudinal analyses of the existing HEMO Study database. SETTING AND PARTICIPANTS: 1,827 HEMO Study participants. PREDICTOR: Serum alkaline phosphatase level. OUTCOME AND MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: Based on the median serum alkaline phosphatase of 97 IU/l, participants were divided into low (< 97 IU/l) and high (> or = 97 IU/l) serum alkaline phosphatase groups. The lower serum alkaline phosphatase group was associated with older age, male gender, non-black race and shorter dialysis years as well as higher serum calcium, higher serum calcium-phosphorus product and lower parathyroid hormone levels. Mean serum liver enzyme values were in the normal range in both groups, but the high alkaline phosphatase group had slightly higher values. In a multivariate time-dependent Cox model using baseline and follow-up values of serum alkaline phosphatase levels, adjusted for demographics, HEMO Study groups, comorbidity, bone metabolism parameters and liver enzymes, each doubling of serum alkaline phosphatase was significantly associated with increased hazard of all-cause (hazard ratio 1.44, 95% CI 1.30 - 1.59) and cardiovascular mortality (hazard ratio 1.35, 95% CI 1.16 - 1.57). LIMITATIONS: Nonstandardized measurements of alkaline phosphatase. CONCLUSIONS: Serum alkaline phosphatase is associated with increased mortality in hemodialysis patients, independent of bone metabolism parameters and liver enzymes. Alkaline phosphatase might be a potential therapeutic target in hemodialysis patients.