Ferric citrate hydrate for the treatment of hyperphosphatemia in nondialysis-dependent CKD
Keitaro Yokoyama1, Hideki Hirakata, Takashi Akiba
1Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan;, †Japanese Red Cross, Fukuoka Hospital, Fukuoka, Japan;, ‡Department of Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan;, §Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan;, ‖Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan;, ¶Department of Hematology, Nephrology and Rheumatology, Akita University, Akita, Japan;, *Kitasato University East Hospital Clinical Trial Center, Sagamihara, Japan, ††Denver Nephrologists, PC, Denver, Colorado.
Insights
Ferric citrate hydrate effectively lowers serum phosphate and FGF-23 in CKD patients. This iron-based binder also improved iron levels with a similar safety profile to placebo.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Hyperphosphatemia is a common complication in patients with chronic kidney disease (CKD).
- Phosphate binders are crucial for managing hyperphosphatemia in CKD.
- Ferric citrate hydrate is an emerging iron-based phosphate binder.
Purpose of the Study:
- To evaluate the efficacy and safety of ferric citrate hydrate in non-dialysis-dependent CKD patients.
- To assess the impact of ferric citrate hydrate on serum phosphate levels.
- To determine changes in fibroblast growth factor-23 (FGF-23) and iron parameters.
Main Methods:
- A phase 3, multicenter, randomized, double-blind, placebo-controlled study.
- 90 non-dialysis-dependent CKD patients with elevated serum phosphate were randomized to ferric citrate hydrate or placebo for 12 weeks.
- Primary endpoint: change in serum phosphate; Secondary endpoints: achievement of target phosphate levels, changes in FGF-23, and iron parameters.
Main Results:
- Ferric citrate hydrate significantly reduced serum phosphate compared to placebo (P<0.001).
- 64.9% of patients on ferric citrate hydrate achieved target phosphate levels versus 6.9% on placebo (P<0.001).
- Significant reductions in FGF-23 and improvements in serum iron, ferritin, and transferrin saturation were observed with ferric citrate hydrate.
Conclusions:
- Ferric citrate hydrate is effective in reducing serum phosphate and FGF-23 in non-dialysis-dependent CKD patients.
- The treatment also improved iron status.
- Ferric citrate hydrate demonstrated a comparable safety profile to placebo, with gastrointestinal disorders being the most common adverse events.
Background And Objectives:
Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD.
Design, Setting, Participants, & Measurements:
A phase 3, multicenter, randomized, double blind, placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD. Starting in April of 2011, 90 CKD patients (eGFR=9.21±5.72 ml/min per 1.73 m(2)) with a serum phosphate≥5.0 mg/dl were randomized 2:1 to ferric citrate hydrate or placebo for 12 weeks. The primary end point was change in serum phosphate from baseline to the end of treatment. Secondary end points included the percentage of patients achieving target serum phosphate levels (2.5-4.5 mg/dl) and change in fibroblast growth factor-23 at the end of treatment.
Results:
The mean change in serum phosphate was -1.29 mg/dl (95% confidence interval, -1.63 to -0.96 mg/dl) in the ferric citrate hydrate group and 0.06 mg/dl (95% confidence interval, -0.20 to 0.31 mg/dl) in the placebo group (P<0.001 for difference between groups). The percentage of patients achieving target serum phosphate levels was 64.9% in the ferric citrate hydrate group and 6.9% in the placebo group (P<0.001). Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo (change from baseline [median], -142.0 versus 67.0 pg/ml; P<0.001). Ferric citrate hydrate significantly increased serum iron, ferritin, and transferrin saturation compared with placebo (P=0.001 or P<0.001). Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo. Overall, adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo, with gastrointestinal disorders occurring in 30.0% of ferric citrate hydrate patients and 26.7% of patients receiving placebo.
Conclusion:
In patients with nondialysis-dependent CKD, 12-week treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters.
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