Strict phosphate control toward the normal range may delay or reverse coronary artery calcification (CAC) in patients on hemodialysis (HD), according to new findings from the Japanese EPISODE trial.

“This study is the first to demonstrate that lowering elevated phosphate levels toward the normal range would have a beneficial effect on the progression of CAC even in elderly patients with more calcification, thus, strict phosphate control might improve mortality in this superaging society,” Yoshitaka Isaka, MD, PhD, of Osaka University Graduate School of Medicine in Osaka, Japan, and colleagues reported in the Journal of the American Society of Nephrology.

In the EPISODE  (Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM) trial, investigators randomly assigned 160 adults on dialysis to a strict serum phosphate target of 3.5 to 4.5 mg/dL or a standard target of 5.0 to 6.0 mg/dL using either the noncalcium phosphate binder lanthanum carbonate or sucroferric oxyhydroxide. At 12 months, serum phosphate levels had decreased to 5.13 mg/dL in the lanthanum carbonate group and 5.07 mg/dL in the sucroferric oxyhydroxide group using mean daily doses of 1590 mg and 1168 mg, respectively.

Continue Reading

The percentage change in CAC scores was significantly lower in the strict control than the standard control group over 12 months: median 8.5% vs 21.8%. The investigators observed significant differences in CAC progression among patients 65 years and older (6.5% in strict group vs 21.4% in standard group), but not among younger patients.

Absolute changes in CAC scores also were significantly lower in the strict control than the standard control group: 66.1 vs 125.9. CAC progression did not differ significantly between the phosphate binder arms.

The EPISODE trial included patients with a predialysis serum phosphate level of at least 5.0 mg/dL if not previously taking phosphate binders or at least 6.1 mg/dL if taking phosphate binders. The study did not examine changes in low density lipoprotein (LDL) cholesterol, dietary phosphate intake, normalized protein catabolism rate, or body mass index. Patients with severe hyperparathyroidism (a predialysis serum intact parathyroid hormone exceeding 800 pg/mL) were excluded.

Serious adverse events occurred in similar proportions of the strict and standard phosphate control group: 19.2% vs 20.5%, respectively. The most common adverse event was diarrhea. Several patients had phosphate levels less than 3.5 mg/dL, but none experienced related adverse events.

“EPISODE is the first completed trial to address the fundamental question of whether a strategy of guideline-endorsed phosphate normalization, as executed in the strict arm of the trial, has a favorable effect on cardiovascular health,” Ron Wald, MD, of St. Michael’s Hospital in Toronto and Michael W. Walsh, MD, of McMaster University in Hamilton Ontario, Canada, stated in an accompanying editorial.

Disclosure: This clinical trial was supported by Kissei Pharmaceutical Co. Ltd. Please see the original reference for a full list of authors’ disclosures.


Isaka Y, Hamano T, Fujii H, et al. Optimal phosphate control related to coronary artery calcification in dialysis patients. Published online February 5, 2021. J Am Soc Nephrol. doi:10.1681/ASN.2020050598

Wald R, Walsh MW. In search of the optimal target for phosphate control: episode 1. Published online February 5, 2021. J Am Soc Nephrol. doi:10.1681/ASN.2021010027