Combined Alkaline Phosphatase and Phosphorus Levels as a Predictor of Mortality in Maintenance Hemodialysis Patients

Hyperphosphatemia-induced vascular calcification and higher alkaline phosphatase (ALP) levels-related high-turnover bone diseases are linked to mortality among patients with chronic kidney disease (CKD). Nonetheless, no large epidemiological study in patients with CKD has been conducted to investigate the interaction and joint effect of hyperphosphatemia and higher ALP levels on mortality. We analyzed 11,912 maintenance hemodialysis patients from January 2005 to December 2010. Unadjusted and adjusted hazard ratios (aHRs) of death were calculated for different categories of serum phosphorus and ALP using the Cox regression model. The modification effect between serum phosphorus and ALP on mortality was determined using an interaction product term. Both hypophosphatemia (< 3.0mg/dL) and hyperphosphatemia (> 7.0mg/dL) were associated with incremental risks of death (aHR: 1.25 [95% confidence intervals (CIs): 1.09-1.44], and 1.15 [95% CI: 1.01-1.31], respectively) compared to the lowest hazard ratio (HR) group (5mg/dL <= phosphorus< 6mg/dL). ALP levels were linearly associated with incremental risks for death (aHR: 1.58 [95% CI: 1.41-1.76] for the category of ALP> 150U/L). In the stratified analysis, patients with combined higher ALP (> 150U/L) and hyperphosphatemia (> 7.0mg/dL) had the greatest mortality risk (aHR: 2.25 [95% CI: 1.69-2.98] compared to the lowest HR group (ALP <= 60 U/L and 4mg/dL <= phosphorus< 5mg/ dL). Although the effect of hyperphosphatemia on mortality seemed stronger in higher ALP levels, the interaction was not statistically significant (P = 0.22). The association between serum phosphorus levels and mortality was not limited to higher ALP levels. Regardless of serum ALP levels, we may control serum phosphorus levels merely toward the normal range. While considering the joint effect of ALP and hyperphosphatemia on mortality, the optimal phosphorus range should be stricter.