Alkalosis and Dialytic Clearance of Phosphate Increases Phosphatase Activity: A Hidden Consequence of Hemodialysis

Extracellular pyrophosphate is a potent endogenous inhibitor of vascular calcification, which is degraded by alkaline phosphatase (ALP) and generated by hydrolysis of ATP via ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1). ALP activity (as routinely measured in clinical practice) represe...

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Bibliographic Details
Published in:PloS one 2016-07, Vol.11 (7), p.e0159858-e0159858
Main Authors: Villa-Bellosta, Ricardo, González-Parra, Emilio, Egido, Jesús
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Aged
Aged, 80 and over
Alkaline phosphatase
Alkaline Phosphatase - metabolism
Alkalosis
Alkalosis - blood
Alkalosis - etiology
Alkalosis - metabolism
ATP
Bioassays
Biological assays
Biology and Life Sciences
Biomedical research
Calcification
Calcification (ectopic)
Calcification (Physiology)
Diabetes
Dialysis
Enzyme Activation
Female
Health aspects
Hemodialysis
Homeostasis
Humans
Hydrogen
Hydrogen ions
Hydrogen-Ion Concentration
Hydrolysis
Male
Medicine and Health Sciences
Metabolic disorders
Metabolism
Middle Aged
Mortality
pH effects
Phosphatase
Phosphatases
Phosphates
Phosphates - blood
Phosphates - metabolism
Phosphodiesterase
Phosphoric Monoester Hydrolases - blood
Phosphoric Monoester Hydrolases - metabolism
Phosphorus
Physical Sciences
Physiology
Pyrophosphatase
Renal Dialysis - adverse effects
Risk factors
Rodents
Smooth muscle
Synthesis
Toxins
Urea
Vascular Calcification
Vascular diseases
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Summary:Extracellular pyrophosphate is a potent endogenous inhibitor of vascular calcification, which is degraded by alkaline phosphatase (ALP) and generated by hydrolysis of ATP via ectonucleotide pyrophosphatase/phosphodiesterase 1 (eNPP1). ALP activity (as routinely measured in clinical practice) represents the maximal activity (in ideal conditions), but not the real activity (in normal or physiological conditions). For the first time, the present study investigated extracellular pyrophosphate metabolism during hemodialysis sessions (including its synthesis via eNPP1 and its degradation via ALP) in physiological conditions. 45 patients in hemodialysis were studied. Physiological ALP activity represents only 4-6% of clinical activity. ALP activity increased post-hemodialysis by 2% under ideal conditions (87.4 ± 3.3 IU/L vs. 89.3 ± 3.6 IU/L) and 48% under physiological conditions (3.5 ± 0.2 IU/L vs. 5.2 ± 0.2 IU/L). Pyrophosphate synthesis by ATP hydrolysis remained unaltered post-hemodialysis. Post-hemodialysis plasma pH (7.45 ± 0.02) significantly increased compared with the pre-dialysis pH (7.26 ± 0.02). The slight variation in pH (~0.2 units) induced a significant increase in ALP activity (9%). Addition of phosphate in post-hemodialysis plasma significantly decreased ALP activity, although this effect was not observed with the addition of urea. Reduction in phosphate levels and increment in pH were significantly associated with an increase in physiological ALP activity post-hemodialysis. A decrease in plasma pyrophosphate levels (3.3 ± 0.3 μmol/L vs. 1.9 ± 0.1 μmol/L) and pyrophosphate/ATP ratio (1.9 ± 0.2 vs. 1.4 ± 0.1) post-hemodialysis was also observed. Extraction of uremic toxins, primarily phosphate and hydrogen ions, dramatically increases the ALP activity under physiological conditions. This hitherto unknown consequence of hemodialysis suggests a reinterpretation of the clinical value of this parameter.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0159858