Can Serum Levels of Alkaline Phosphatase and Phosphate Predict Cardiovascular Diseases and Total Mortality in Individuals with Preserved Renal Function? A Systemic Review and Meta-Analysis

Abstract

BackgroundIt is demonstrated that elevated serum levels of alkaline phosphatase (ALP) and phosphate indicate a higher risks of cardiovascular disease (CVD) and total mortality in population with chronic kidney disease (CKD), but it remains unclear whether this association exists in people with normal or preserved renal function.MethodClinical trials were searched from Embase and PubMed from inception to 2013 December using the keywords “ALP”, “phosphate”, “CVD”, “mortality” and so on, and finally 24 trials with a total of 147634 patients were included in this study. Dose-response and semi-parametric meta-analyses were performed.ResultsA linear association of serum levels of ALP and phosphate with risks of coronary heart disease (CHD) events, CVD events and deaths was identified. The relative risk(RR)of ALP for CVD deaths was 1.02 (95% confidence interval [CI], 1.01–1.04). The RR of phosphate for CVD deaths and events was 1.05 (95% CI, 1.02–1.09) and 1.04 (95% CI: 1.03–1.06), respectively. A non-linear association of ALP and phosphate with total mortality was identified. Compared with the reference category of ALP and phosphate, the pooled RR of ALP for total mortality was 1.57 (95% CI, 1.27–1.95) for the high ALP group, while the RR of phosphate for total mortality was 1.33 (95% CI, 1.21–1.46) for the high phosphate group. It was observed in subgroup analysis that higher levels of serum ALP and phosphate seemed to indicate a higher mortality rate in diabetic patients and those having previous CVD. The higher total mortality rate was more obvious in the men and Asians with high ALP.ConclusionA non-linear relationship exists between serum levels of ALP and phosphate and risk of total mortality. There appears to be a positive association of serum levels of ALP/phosphate with total mortality in people with normal or preserved renal function, while the relationship between ALP and CVD is still ambiguous.

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality

“…There is no standard cutoff for evaluating the effect of elevated AlkP. We selected a cutoff of 1.5 times approximate upper limit of normal, or 180 IU/L, which has been shown in a large meta-analysis to be well within a region indicating increased mortality [15], while including a meaningful percentage of the study population.…”

“…Serum AlkP activity is elevated in hepatobiliary and bone diseases. In a recent meta-analysis of a heterogeneous population, including healthy subjects, patients with cardiovascular morbidity, and elderly patients, AlkP was shown to be a prognostic marker for mortality [15].…”

Investigation of hazardous chemicals exposure on some liver function enzymes using serum and saliva of Iraqi's students

“…ALP (alkaline phosphatase; EC 3.1.3.1) is an enzyme existing in the cells that lining the biliary ducts of the liver, bone, placenta and other tissues. It hydrolyzes phosphate esters with the subsequent releases of inorganic phosphate (Li, Xu, Fan, Wang, & Xiao, 2014). It has several isoenzymes formed by various cells types within alveolar bone and/or salivary glands (Chapple, Garner, Saxby, Moscrop, & Matthews, 1999).…”

“…The main roles of ALP are anti-inflammatory and antithrombotic, also involved in immunological process (Dufour et al, 2000b). It is well known that the inflammation of the hepatocytes plasma membrane is accompanied with the releasing of ALP in circulation (Li et al, 2014).…”

Klotho/FGF23 axis mediates high phosphate‐induced vascular calcification in vascular smooth muscle cells via Wnt7b/β‐catenin pathway

“…Among the various causes in CKD, abnormal deposition of calcium phosphate (Pi) salt is most closely related to VC . It has been proved that elevated serum Pi is a risk factor for VC and cardiovascular mortality and morbidity among CKD populations in clinical studies . Therefore, it is of great significance to study the specific molecular mechanism of VSMCs calcification induced by high phosphorus in CKD.…”