Serum Alkaline Phosphatase Predicts Mortality among Maintenance Hemodialysis Patients

Abstract

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 Ն120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P Ͻ 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 Ͼ120 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. 19: 219319: -220319: , 200819: . doi: 10.1681 In advanced chronic kidney disease (CKD; stages 3 through 5), secondary hyperparathyroidism (SHPT), along with renal osteodystrophy, is common and may be associated with abnormal mineral metabolism and/or abnormal serum or tissue mineral levels, vascular calcifications, and poor survival, espe- contributed to the study design and manuscript preparation and reviewed and approved the final manuscript. J Am Soc Nephrol

Alkaline Phosphatase and Mortality in Patients on Peritoneal Dialysis

“…Our study revealed that total serum ALP levels were associated with higher all-cause and cardiovascular mortality in PD patients, independent of serum calcium, phosphorus, iPTH, and liver enzymes (AST and ALT). It was reported that bone mineral disease characteristics are different in PD and HD (9) and that bone microarchitecture is more severely affected in patients on HD than patients receiving PD (8); however, our study indicated that the association between ALP and mortality in PD patients is similar with the previous study in HD patients (6).…”

“…Another analysis of the Dialysis Outcomes and Practice Patterns Study database showed that elevated serum ALP levels were associated with higher risk of hospitalization and death in HD patients, independent of serum calcium, phosphorus, and PTH levels, without including adjustment for liver function (5). Subsequently, using the DaVita and Hemodialysis Study databases, researchers found that high serum ALP levels in HD patients, adjusted for serum calcium, phosphorus, PTH, and liver enzymes, were indeed associated with higher mortality (6,7). However, little is known about PD patients.…”

“…In nondialysis-dependent CKD patients, higher ALP levels were associated with higher risk of ESRD and all-cause mortality (2)(3)(4). Similarly, in maintenance hemodialysis (HD) patients, elevated ALP levels were also associated with higher risk of mortality, independent of liver function and bone metabolism parameters (5)(6)(7).…”

Serum Alkaline Phosphatase and Phosphate and Risk of Mortality and Hospitalization

“…In patients with ESRD and in the general population, higher serum levels of AlkPhos and phosphate are associated with increased all-cause and cardiovascular mortality (5)(6)(7)(8)(9)(10)(11)(12)(13). Recent studies support the hypothesis that these associations are mediated by vascular calcification (14,15), although medial calcification is seen almost exclusively in patients with advanced kidney disease and diabetes and not in the general population (16).…”

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

“…Lomashvili et al (5) reported that vascular damage can induce expression of tissuenonspecific alkaline phosphatase (AlkPhos), which per se hydrolyzes and inactivates inorganic pyrophosphates, a process that can enhance vascular calcification. We recently showed that higher serum AlkPhos levels in maintenance hemodialysis (MHD) patients were independently associated with increased all-cause and cardiovascular mortality in approximately 74,000 MHD patients, even after adjustment for surrogates of nutrition, inflammation, minerals, serum parathyroid hormone (PTH), and liver enzymes (10). Nevertheless, the pathophysiologic link between increased AlkPhos level and mortality in MHD patients is not clear.…”