title: Combined alkaline phosphatase and phosphorus levels as a predictor of mortality in maintenance hemodialysis patients.
abstract: 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 (<3.0 mg/dL) and hyperphosphatemia (>7.0 mg/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 (5 mg/dL ≤ phosphorus<6 mg/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>150 U/L). In the stratified analysis, patients with combined higher ALP (>150 U/L) and hyperphosphatemia (>7.0 mg/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 4 mg/dL ≤ phosphorus<5 mg/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.
authors.affiliation: Divison of Nephrology (J-FC, Y-SP, S-PH, M-FP, H-YC, H-YW, J-YY), Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City; Graduate Institute of Basic Medicine (J-FC), Fu Jen Catholic University; and Department of Nursing (Y-FF), Jiate Excelsior Co, Ltd, Taipei, Taiwan.
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Chang
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Feng
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Peng
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Hsu
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Pai
authors.forename: Hung-Yuan
authors.initials: HY
authors.lastname: Chen
authors.forename: Hon-Yen
authors.initials: HY
authors.lastname: Wu
authors.forename: Ju-Yeh
authors.initials: JY
authors.lastname: Yang
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood*; D006435:Renal Dialysis / Q000401:mortality*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000401:mortality* / Q000628:therapy; D018570:Risk Assessment; D012709:Serum Albumin / Q000032:analysis; D013624:Taiwan / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D012709:Serum Albumin; D010758:Phosphorus; D002784:Cholesterol; D003404:Creatinine; D000469:Alkaline Phosphatase