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Serum Alkaline Phosphatase and Mortality in African Americans with Chronic Kidney Disease

Srinivasan Beddhu^*,, Xiulian Ma, Bradley Baird, Alfred K. Cheung^*,, and Tom Greene^*,

^* Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah; and Department of Medicine, University of Utah, Salt Lake City, Utah

Correspondence: Dr. Srinivasan Beddhu,85 North Medical Drive East, Room 201, Salt Lake City, UT 84112. Phone: 801-585-3810; Fax: 801-581-4750; E-mail: Srinivasan.beddhu{at}hsc.utah.edu

Background and objectives: Serum alkaline phosphatase has been associated with increased mortality in hemodialysis patients but its associations with mortality in chronic kidney disease (CKD) stages III and IV are unknown.

Design, settings, participants & measurements: In 1094 participants in the African-American Study of Kidney Disease and Hypertension (AASK) database, the associations of serum alkaline phosphatase with mortality and cardiovascular events were examined in Cox models.

Results: The mean (±SD) age was 54 ± 11 yr, and 61% were men. The median alkaline phosphatase was 80 IU/L, and interquartile range was 66 to 97 IU/L. The mean follow-up was 4.6 yr. There were 105 (9.6%) all-cause deaths and 149 (13.6%) cardiovascular events. Each doubling of serum alkaline phosphatase was significantly associated with increased hazard [hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.08 –2.36] of all-cause mortality adjusted for demographics, drug and blood pressure groups, and comorbidity. With further adjustment for liver function tests as well as serum calcium and phosphorus, each doubling of serum alkaline phosphatase remained significantly associated with increased mortality (HR 1.55, 95% CI 1.03 to 2.33). Serum alkaline phosphatase was not significantly associated with increased risk of cardiovascular events.

Conclusions: Independent of liver function tests and serum calcium and phosphorus, higher levels of serum alkaline phosphatase are associated with increased mortality in the CKD population. Further studies are warranted to identify the potential mechanisms for this association.