Effects of acute variation of dialysate calcium concentrations on arterial stiffness and aortic pressure waveform

Abstract

Background: Abnormal mineral metabolism in chronic kidney disease plays a critical role in vascular calcification and arterial stiffness. The impact of presently used dialysis calcium concentration (D(Ca)) on arterial stiffness and aortic pressure waveform has never been studied. The aim of the present study is to evaluate, in haemodialysis (HD) patients, the impact of acute modification of D(Ca) on arterial stiffness and central pulse wave profile (cPWP). Method. A randomized Latin square cross-over study was used to evaluate the three different concentrations of D(Ca) (1.00, 1.25 and 1.50 mmol/L) during the second HD of the week for 3 consecutive weeks. Subjects returned to their baseline D(Ca) for the following two treatments, allowing for a 7-day washout period between each experimental HD. cPWP, carotido-radial (c-r) and carotido-femoral (c-f) pulse wave velocities (PWV), plasma level of ionized calcium (iCa) and intact parathyroid hormone (PTH) were measured prior to and immediately after each experimental HD session. Data were analysed by the general linear model for repeated measures and by the general linear mixed model.

Results: Eighteen patients with a mean age of 48.9 +/- 18 years and a median duration of HD of 8.7 months (range 1-87 months) completed the study. In post-HD, iCa decreased with D(Ca) of 1.00 mmol/L (-0.14 +/- 0.04 mmol/L, P < 0.001), increased with a D(Ca) of 1.50 mmol/L (0.10 +/- 0.06 mmol/L, P < 0.001) but did not change with a D(Ca) of 1.25 mmol/L. Tests of within-subject contrast showed a linear relationship between higher D(Ca) and a higher post-HD Deltac-f PWV, Deltac-r PWV and Deltamean BP (P < 0.001, P = 0.008 and P = 0.002, respectively). Heart rate-adjusted central augmentation index (AIx) decreased significantly after HD, but was not related to D(Ca). The timing of wave refection (Tr) occurred earlier after dialysis resulting in a linear relationship between higher D(Ca) and post-HD earlier Tr (P < 0.044). In a multivariate linear-mixed model for repeated measures, the percentage increase in c-f PWV and c-r PWV was significantly associated with the increasing level of iCa, whereas the increasing level of DeltaMBP was not significant. In contrast, the percentage decrease in Tr (earlier wave reflection) was determined by higher DeltaMBP and higher ultrafiltration, whereas the relative change in AIx was inversely determined by the variation in the heart rate and directly by DeltaMBP.

Conclusion: We conclude that D(ca) and acute changes in the serum iCa concentration, even within physiological range, are associated with detectable changes of arterial stiffness and cPWP. Long-term studies are necessary to evaluate the long-term effects of D(Ca) modulation on arterial stiffness.

Fig. 1

Central pulse wave profile. The central pulse wave profile can be broken into the following parameters: first peak of pressure (P1), second peak of pressure (P2), time at P1 (T1), time at P2 (T2), time of return of the reflection wave (Tr), diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP).

Fig. 2

Mean pre- and post-haemodialysis central pressure waveform. Using the mean pressure points at corresponding time points of each patient (n = 18), the group's central pulse wave profile (cPWP) was constructed for each treatment group. The solid line and dotted lines indicate the pre- and post-HD cPWP, respectively. The top, middle and lower panels, respectively, refer to dialysate calcium concentrations of 1.00, 1.25 and 1.50 mmol/L.