Plasma pyrophosphate and vascular calcification in chronic kidney disease

Abstract

Background: Pyrophosphate (PPi) is a potent inhibitor of vascular calcification and may be deficient in renal failure. We sought to determine whether plasma PPi is affected by dialysis or the mode of dialysis and whether it correlates with vascular calcification.

Methods: PPi was measured in plasma samples stored from a recent study of vascular calcification in 54 HD patients, 23 peritoneal dialysis (PD) patients and 38 patients with stage 4 chronic kidney disease (CKD). Calcification was quantified in a standardized section of the superficial femoral artery using computed tomography, and PPi was measured by enzyme assay, at both baseline and 1 year.

Results: Baseline plasma PPi was weakly correlated with age and serum phosphate, but not with alkaline phosphatase activity or other biochemical parameters, and did not differ between HD, PD and CKD patients. Both baseline calcification score and change in the calcification score at 1 year decreased with increasing quartiles of plasma PPi. In a multivariate analysis, plasma PPi was independently correlated with baseline calcification (P = 0.039) and the change in calcification (P = 0.029).

Conclusion: Plasma PPi is negatively associated with vascular calcification in end-stage renal disease (ESRD) and CKD but is not affected by dialysis, the mode of dialysis or nutritional or inflammatory status. Although these data are consistent with an inhibitory effect of PPi on vascular calcification, further studies are needed to establish a causal role.

Fig. 1

Correlation between serum phosphorus and plasma pyrophosphate at baseline. The correlation coefficient is 0.23, P < 0.02.

Fig. 2

Mean baseline vascular calcification score in increasing quartiles of baseline plasma pyrophosphate. The mean PPi levels in each quartile were 1.49, 2.60, 3.34 and 5.04 μM. Error bars indicate standard error.

Fig. 3

Mean 1-year vascular calcification score in increasing quartiles of 1-year plasma pyrophosphate. Error bars indicate standard error. P = 0.005 by the Kruskal–Wallis test.

Fig. 4

Mean change in vascular calcification score in increasing quartiles of baseline plasma pyrophosphate. Error bars indicate standard error.