TY - JOUR
T1 - The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients
T2 - Results from Prespecified Analyses of a Randomized Clinical Trial
AU - Van Buren, Peter N.
AU - Lewis, Julia B.
AU - Dwyer, Jamie P.
AU - Greene, Tom
AU - Middleton, John
AU - Sika, Mohammed
AU - Umanath, Kausik
AU - Abraham, Josephine D.
AU - Arfeen, Shahabul S.
AU - Bowline, Isai G.
AU - Chernin, Gil
AU - Fadem, Stephen Z.
AU - Goral, Simin
AU - Koury, Mark
AU - Sinsakul, Marvin V.
AU - Weiner, Daniel E.
N1 - Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels 6.0 mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04 ± 1.99 [SD] vs -2.18 ± 2.25 mg/dL, respectively; P = 0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22 ± 0.90 vs 0.31 ± 0.95 mg/dL; P = 0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1 ± 399.8 vs -152.7 ± 392.1 pg/mL; P = 0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open-label study, few peritoneal dialysis patients. Conclusions Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
AB - Background Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. Study Design 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. Setting & Participants Maintenance dialysis patients with serum phosphorus levels 6.0 mg/dL after washout of prior phosphate binders. Intervention 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). Outcomes Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. Measurements Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. Results There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04 ± 1.99 [SD] vs -2.18 ± 2.25 mg/dL, respectively; P = 0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22 ± 0.90 vs 0.31 ± 0.95 mg/dL; P = 0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1 ± 399.8 vs -152.7 ± 392.1 pg/mL; P = 0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. Limitations Open-label study, few peritoneal dialysis patients. Conclusions Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
KW - Index Words Hemodialysis
KW - adverse events
KW - calcium acetate
KW - end-stage renal disease (ESRD)
KW - ferric citrate
KW - hyperphosphatemia
KW - mineral bone disease
KW - phosphate binder
KW - protein-energy wasting (PEW)/inflammation
KW - safety
KW - sevelamer carbonate
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U2 - 10.1053/j.ajkd.2015.03.013
DO - 10.1053/j.ajkd.2015.03.013
M3 - Article
C2 - 25958079
AN - SCOPUS:84939564696
SN - 0272-6386
VL - 66
SP - 479
EP - 488
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -