title: Alkalinization potentiates vascular calcium deposition in an uremic milieu.
abstract: BACKGROUND
  Vascular calcification is a serious complication of chronic kidney disease. Acid-base balance is a relevant, albeit somewhat forgotten factor in the regulation of calcium deposition. Hemodialysis patients undergo repeated episodes of alkaline loading from the dialysate, resulting in prolonged alkalinization. We have hypothesized that extracellular alkalinization may promote vascular calcification.
  
  
  METHODS
  Primary cultures of vascular smooth muscle cells were induced to calcify by the phosphate donor beta-glycerophosphate, in the presence of normal or uremic sera from hemodialysis patients and at different pH conditions. The influence of sodium bicarbonate supplementation for 2 months on aorta calcification was studied in 5/6 nephrectomized uremic rats.
  
  
  RESULTS
  Uremic serum increased vascular smooth muscle cell calcification (twofold over nonuremic human serum at day 12, p<0.001). Alkalinization of the extracellular medium also increased vascular smooth muscle cell calcification. Increasing the extracellular pH from 7.42 to 7.53 resulted in a 2.5-fold increase in calcium accumulation at day 12 (p<0.05). In vivo, arterial calcification was significantly higher in alkalinized uremic animals (aorta calcification index, uremic + sodium bicarbonate, 164 +/- 57 units, vs. uremic + vehicle, 56 +/- 14 units; p<0.01).
  
  
  CONCLUSIONS
  Alkalinization increases vascular calcification in cultured cells and uremic rats. These data may be used to optimize dialysate composition and the degree of alkalinization in calcification-prone individuals with advanced renal disease.
authors.affiliation: Laboratory of Nephrology and Hypertension, Jiménez Díaz-Capio Fundation, Universidad Autónoma de Madrid, Queen Sophie Renal Research Institute, Madrid, Spain.
authors.forename: Alain J
authors.initials: AJ
authors.lastname: de Solis
authors.forename: Francisco R
authors.initials: FR
authors.lastname: González-Pacheco
authors.forename: Juan J P
authors.initials: JJ
authors.lastname: Deudero
authors.forename: Fernando
authors.initials: F
authors.lastname: Neria
authors.forename: Marta
authors.initials: M
authors.lastname: Albalate
authors.forename: Vladimir
authors.initials: V
authors.lastname: Petkov
authors.forename: Luis
authors.initials: L
authors.lastname: Susanibar
authors.forename: Ruth
authors.initials: R
authors.lastname: Fernandez-Sanchez
authors.forename: Olalla
authors.initials: O
authors.lastname: Calabia
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Carlos
authors.initials: C
authors.lastname: Caramelo
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009392:Nephrectomy / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000209:etiology / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D002118:Calcium