Alkalinization potentiates vascular calcium deposition in an uremic milieu.
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.
de Solis
Alain J
AJ
Laboratory of Nephrology and Hypertension, Jiménez Díaz-Capio Fundation, Universidad Autónoma de Madrid, Queen Sophie Renal Research Institute, Madrid, Spain.
González-Pacheco
Francisco R
FR
Deudero
Juan J P
JJ
Neria
Fernando
F
Albalate
Marta
M
Petkov
Vladimir
V
Susanibar
Luis
L
Fernandez-Sanchez
Ruth
R
Calabia
Olalla
O
Ortiz
Alberto
A
Caramelo
Carlos
C
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*
D001639:Bicarbonates; D002118:Calcium