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Clinical Research
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Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients

Yoshitaka Isaka, Takayuki Hamano, Hideki Fujii, Yoshihiro Tsujimoto, Fumihiko Koiwa, Yusuke Sakaguchi, Ryoichi Tanaka, Noriyuki Tomiyama, Fuminari Tatsugami and Satoshi Teramukai
JASN March 2021, 32 (3) 723-735; DOI: https://doi.org/10.1681/ASN.2020050598
Yoshitaka Isaka
1Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
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Takayuki Hamano
1Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
2Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Hideki Fujii
3Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine
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Yoshihiro Tsujimoto
4Division of Internal Medicine, Medical Corporation Aijinkai Inoue Hospital, Suita, Japan
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Fumihiko Koiwa
5Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan
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Yusuke Sakaguchi
1Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
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Ryoichi Tanaka
6Department of Radiology, Iwate Medical University School of Medicine, Shiwa, Japan
7Division of Dental Radiology, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry, Shiwa, Japan
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Noriyuki Tomiyama
8Department of Radiology, Osaka University Graduate School of Medicine, Suita, Japan
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Fuminari Tatsugami
9Department of Diagnostic Radiology, Hiroshima University, Hiroshima, Japan
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Satoshi Teramukai
10Department of Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Significance Statement

Hyperphosphatemia has been reported to be associated with severity of coronary artery calcification (CAC), a predictor of all-cause mortality in incident patients on hemodialysis. However, the optimal phosphate range in such patients remains unknown. The authors conducted a randomized study to compare the effects on CAC progression of two types of noncalcium-based phosphate binders (sucroferric oxyhydroxide or lanthanum carbonate) and of two different phosphate target ranges. The percentage change in CAC score in a strict phosphate control group (3.5–4.5 mg/dl) was significantly lower than that in a standard phosphate control group (5.0–6.0 mg/dl). The phosphate binders did not differ in their effects on CAC progression. Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying CAC progression in patients on hemodialysis.

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

  • hyperphosphatemia
  • dialysis
  • coronary calcification
  • phosphate binders
  • Copyright © 2021 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 32 (3)
Journal of the American Society of Nephrology
Vol. 32, Issue 3
March 2021
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Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients
Yoshitaka Isaka, Takayuki Hamano, Hideki Fujii, Yoshihiro Tsujimoto, Fumihiko Koiwa, Yusuke Sakaguchi, Ryoichi Tanaka, Noriyuki Tomiyama, Fuminari Tatsugami, Satoshi Teramukai
JASN Mar 2021, 32 (3) 723-735; DOI: 10.1681/ASN.2020050598

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Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients
Yoshitaka Isaka, Takayuki Hamano, Hideki Fujii, Yoshihiro Tsujimoto, Fumihiko Koiwa, Yusuke Sakaguchi, Ryoichi Tanaka, Noriyuki Tomiyama, Fuminari Tatsugami, Satoshi Teramukai
JASN Mar 2021, 32 (3) 723-735; DOI: 10.1681/ASN.2020050598
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Keywords

  • hyperphosphatemia
  • dialysis
  • coronary calcification
  • phosphate binders

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