Hydrolysis of Extracellular Pyrophosphate increases in post-hemodialysis plasma

Vascular calcification (VC) is associated with significant morbidity and mortality of dialysis patients. 
Previous studies showed an association between loss of plasma pyrophosphate and VC. Moreover, loss 
of pyrophosphate occurs during dialysis in this population, suggesting that therapeutic approaches 
that prevent reduction of plasma pyrophosphate levels during dialysis could improve the quality 
of life of dialysis patients. This study found that pyrophosphate hydrolysis was 51% higher in post- 
than pre-dialysis plasma. Dialysis sessions modified the kinetic behavior of alkaline phosphatase, 
increasing its Vmax and reducing its Km, probably due to the elimination of uremic toxins during dialysis. 
At least 75% of alkaline phosphatase activity in human plasma was found to depend on a levamisole
sensitive enzyme probably corresponding to tissue non-specific alkaline phosphatase (TNAP). Dialysis 
increased total plasma protein concentration by 14% and reduced TNAP enzyme by 20%, resulting 
in an underestimation of pyrophosphate hydrolysis in post-dialysis plasma. Levamisole inhibited 
TNAP activity (IC50, 7.2 µmol/L), reducing pyrophosphate hydrolysis in plasma and increasing plasma 
pyrophosphate availability. Alkaline phosphatase is also found in many tissues and cells types; 
therefore, our results in plasma may be indicative of changes in phosphatase activity in other locations 
that collectively could contribute significantly to pyrophosphate hydrolysis in vivo. In conclusion, these 
f
indings demonstrate that dialysis increases pyrophosphate hydrolysis, which, taken together with 
previously reported increases in alkalization and calcium ion levels in post-dialysis plasma, causes VC 
and could be prevented by adding calcification inhibitors during dialysis