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Prognostic Importance of Serum Alkaline Phosphatase in CKD Stages 3–4 in a Clinical Population
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  • Description:

    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.


    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.


    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.


    Single center observational study, lack complete data including PTH for all study participants and attrition bias.


    Higher serum ALP levels in CKD stages 3–4 were independently associated with all-cause mortality and ESRD.

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  • Funding:
    1R39OT22056/OT/OSTLTS CDC HHS/United States
    DK094112/DK/NIDDK NIH HHS/United States
    KL2 RR024990/RR/NCRR NIH HHS/United States
    P60MD00265/MD/NIMHD NIH HHS/United States
    R01 DK085185/DK/NIDDK NIH HHS/United States
    R34 DK094112/DK/NIDDK NIH HHS/United States
    RR024990/RR/NCRR NIH HHS/United States
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