Alkalinization potentiates vascular calcium deposition in an uremic milieu

J Nephrol. Sep-Oct 2009;22(5):647-53.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium
  • Animals
  • Aorta / cytology
  • Aorta / metabolism
  • Bicarbonates / metabolism*
  • Bicarbonates / pharmacology
  • Calcium / metabolism*
  • Cattle
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Nephrectomy / adverse effects
  • Rats
  • Rats, Wistar
  • Uremia / etiology
  • Uremia / metabolism*


  • Bicarbonates
  • Calcium