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Serum Alkaline Phosphatase Predicts Mortality among Maintenance Hemodialysis Patients

Deborah L. Regidor^*, Csaba P. Kovesdy, Rajnish Mehrotra^,, Mehdi Rambod^*, Jennie Jing^*, Charles J. McAllister^||, David Van Wyck^||,¶, Joel D. Kopple^,,** and Kamyar Kalantar-Zadeh^*,

^* Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Salem VA Medical Center, Salem, Virginia; ^|| DaVita, Inc., El Segundo, California; ^¶ Departments of Medicine and Surgery, Arizona Center on Aging, Arizona Health Sciences Center, Tucson, Arizona; and Departments of ^** Family and Population Health and Epidemiology, UCLA School of Public Health, Los Angeles, California

Correspondence: Dr. Kamyar Kalantar-Zadeh, Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910. Phone: 310-222-3891; Fax: 310-782-1837; E-mail: kamkal{at}ucla.edu

Received for publication January 5, 2008. Accepted for publication June 13, 2008.

Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos 120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P < 0.001). This association remained among diverse subgroups of hemodialysis patients, including those positive for hepatitis C antibody. A rise in AlkPhos by 10 U/L during the first 6 mo was incrementally associated with increased risk for death during the subsequent 2.5 yr. In summary, high levels of serum AlkPhos, especially >120 U/L, are associated with mortality among hemodialysis patients. Prospective controlled trials will be necessary to test whether serum AlkPhos measurements could be used to improve the management of renal osteodystrophy.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673