title: Alkalosis and Dialytic Clearance of Phosphate Increases Phosphatase Activity: A Hidden Consequence of Hemodialysis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Fundación Instituto de Investigación Sanitaria, Fundación Jiménez Díaz (FIIS-FJD). Madrid, Spain.|Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Villa-Bellosta
authors.affiliation: Renal Division, "Fundación Jiménez Díaz" University Hospital, Madrid Autonomous University, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: González-Parra
authors.affiliation: Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.|Renal Division, "Fundación Jiménez Díaz" University Hospital, Madrid Autonomous University, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D000471:Alkalosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000097:blood / Q000378:metabolism*; D006435:Renal Dialysis / Q000009:adverse effects*; D061205:Vascular Calcification
chemical_list: D010710:Phosphates; D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase; D010744:Phosphoric Monoester Hydrolases