Dissociation between progression of coronary artery calcification and endothelial function in hemodialysis patients: a prospective pilot study

Abstract

Chronic kidney disease profoundly disturbs calcium-phosphate metabolism and predisposes to premature atherosclerosis. Both coronary artery calcification (CAC) and endothelial dysfunction are common in hemodialysis (HD) patients. We hypothesized that a calcium-free phosphate binder would improve endothelial function and delay progression of vascular calcification in HD patients.

Methods: This was a randomized parallel-group trial in HD patients comparing lanthanum carbonate (LC) with a non-LC phosphorus binders control group (non-LC) at a 1 : 1 randomization. CAC was obtained at baseline, 6, and 12 months, and endothelial function (brachial artery flow-mediated dilation - FMD) at baseline and 6 months.

Results: 13 patients were randomized (LC n = 7 and non-LC n = 6). CAC scores (Log ± SE) at baseline were 7.21 ± 0.62 (LC) and 6.07 ± 0.73 (control). CAC increased in the non-LC group (33 ± 17% and 77 ± 22% at 6 and 12 months), but tended to decrease in the LC group (-10 ± 11% and -2 ± 11% at 6 and 12 months). There was statistically less progression in CAC in the LC group compared to control at 6 (p = 0.002) and 12 months (p = 0.003). There was no difference between groups in FMD (p = 0.7). Markers of inflammation did not change significantly.

Conclusion: A slower rate of progression of CAC occurred in the LC group, independent of changes in FMD. This is the first study showing dissociation between progression of CAC and FMD in HD patients. Larger studies are warranted to elucidate the impact of different phosphate sequestration therapies on atherosclerosis in HD patients.

Figure 1.. Phosporus levels at randomization day (post-wash out period), at 1,3,6,9 and 12 months.

Figure 2.. A: Change in CAC LC vs. control: p = 0.02 and 0.003 at 6 and 12 months compared to baseline. B: Coronary artery calcification (log transformed) changes over time, –—— lanthanum; •••••• control.

Figure 3.. LC vs. control: Flow-mediated dilatation (FMD) at baseline and 6 months. Change in FMD from baseline at 6 months from baseline did not differ significantly between groups (p = 0.77).