Prognostic Importance of Serum Alkaline Phosphatase in CKD Stages 3-4 in a Clinical Population

Abstract

Background Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. Study Design Retrospective cohort study. Setting & Participants 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate [eGFR], 15–59 ml/min/1.73 m2) were identified using the Cleveland Clinic Chronic Kidney Disease Registry. CKD was defined as two eGFR values <60 ml/min/1.73 m2 drawn >90 days apart using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Predictor ALP levels measured using the calorimetric assay was examined as quartiles (quartile 1, <66 U/L; Q2, 66–81 U/L; Q3, 82–101 U/L; and Q4, ≥102 U/L) and as a continuous measure. Outcomes & Measurements All-cause mortality and ESRD were ascertained using the Social Security Death Index and US Renal Data System. Results After a median follow up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in the risk for mortality with higher ALP quartiles (Q2, Q3, Q4) when compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications and liver function tests. The highest quartile of ALP was associated with a hazard ratio for ESRD of 1.38 (95% CI, 1.09–1.76). Each 1-standard deviation (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09–1.22) and 16% (95% CI, 1.14–1.18) increased risk of ESRD and mortality respectively. Limitations Single center observational study, lack complete data including PTH for all study participants and attrition bias. Conclusions Higher serum ALP levels in CKD stages 3–4 were independently associated with all-cause mortality and ESRD.

Serum Alkaline Phosphatase Negatively Affects Endothelium-Dependent Vasodilation in Naïve Hypertensive Patients

“…The main action of this enzyme is to catalyze the hydrolysis of the calcification inhibitor pyrophosphate. 1 Pivotal studies conducted in dialysis 2,3 and in end-stage renal disease patients [4][5][6] demonstrated that ALP is linearly associated with all-cause and cardiovascular mortality, similarly to what also observed in patients without overt chronic kidney disease (CKD) 7,8 ; in addition, a significant association between serum ALP and coronary heart disease and total mortality has been previously reported in older men. 9 Recent data showed that mild inflammation and oxidative stress signaling play a key pathogenetic role in the development of vascular mineral deposition of which ALP is a wellestablished marker.…”

“…by guest on May 10, 2018 http://hyper.ahajournals.org/ Downloaded from studies linking this molecule with mortality and cardiovascular events in patients with [4][5][6] or without 7,8 CKD. Taken together, our data are particularly relevant because they demonstrate, for the first time, a significant association between ALP and endothelial dysfunction, an early functional alteration in the continuum of vascular aging and atherosclerotic process.…”

Alkaline Phosphatase and Mortality in Patients on Peritoneal Dialysis

“…Beddhu et al (2) reported that doubling baseline ALP level was associated with a 55% increase in all-cause mortality rate by a post hoc analysis from the African-American Study of Kidney Disease and Hypertension database. Another study including 28,678 patients with CKD stages 3 and 4 found that each 1-SD (42.7 U/L) higher ALP level was associated with 15% and 16% higher risk of ESRD and mortality, respectively, after multivariate adjustment (4). Some studies have examined the association between ALP level and mortality in HD patients.…”

“…Data from the National Health and Nutrition Examination Survey (NHANES) database show a graded independent association between higher ALP levels and mortality in the general population (1). 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).…”

Bone alkaline phosphatase isoforms in chronic kidney disease : mineral and bone disorder

“…The enzymatic differences of the BALP isoforms with respect to PPi and other substrates, described by our group (71), suggest putative differences in the significance of the BALP isoforms for the process of vascular calcification. In CKD, numerous longitudinal and cross-sectional studies have demonstrated an association of ALP with mortality in different CKD populations (78, [173][174][175][176][177][178][179][180][181][182][183][184][185][186][187][188]. This association seems to be independent of PTH, phosphate, and calcium (174,176).…”