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Randomized Controlled Trial
. 2021 Mar;32(3):723-735.
doi: 10.1681/ASN.2020050598. Epub 2021 Feb 5.

Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients

Yoshitaka Isaka  1 , Takayuki Hamano  1   2 , Hideki Fujii  3 , Yoshihiro Tsujimoto  4 , Fumihiko Koiwa  5 , Yusuke Sakaguchi  1 , Ryoichi Tanaka  6   7 , Noriyuki Tomiyama  8 , Fuminari Tatsugami  9 , Satoshi Teramukai  10
Affiliations
Randomized Controlled Trial

Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients

Yoshitaka Isaka et al. J Am Soc Nephrol. 2021 Mar.

Abstract

Background: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges.

Methods: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment.

Results: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores.

Conclusions: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis.

Clinical trial registry name and registration number: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.

Keywords: coronary calcification; dialysis; hyperphosphatemia; phosphate binders.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flow chart of enrollment and randomization. A total of 156 patients were randomly assigned to receive LC or SO (factor 1) in order to reduce serum phosphate levels to two target levels (strict or standard; factor 2). PPS, per protocol set.
Figure 2.
Figure 2.
Changes in laboratory parameters. Shown are trends of the (A and B) serum phosphate levels, (C and D) serum calcium levels, and (E and F) calcium-phosphate concentration product in (A, C, and E) the LC versus SO group and (B, D, and F) the standard versus strict groups and (A) the dose of phosphate binder in the LC and SO groups. The error bars indicate SEMs.
Figure 3.
Figure 3.
Progression of CAC scores. Shown are (A) %CAC change and (B) absolute change of CAC scores in the LC, SO, standard, and strict groups. The effects on %CAC change or absolute change of CAC scores are compared between groups using the Wilcoxon rank-sum test. Data are from the FAS population. (C and D) The change in CAC scores is associated with the change in phosphate levels.
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Comment in

References

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