The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients

Results from Prespecified Analyses of a Randomized Clinical Trial

Peter N. Van Buren, Julia B. Lewis, Jamie P. Dwyer, Tom Greene, John Middleton, Mohammed Sika, Kausik Umanath, Josephine D. Abraham, Shahabul S. Arfeen, Isai G. Bowline, Gil Chernin, Stephen Z. Fadem, Simin Goral, Mark Koury, Marvin V. Sinsakul, Daniel E. Weiner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)479-488
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume66
Issue number3
DOIs
StatePublished - Sep 1 2015

Fingerprint

Minerals
Dialysis
calcium acetate
Randomized Controlled Trials
Phosphates
Maintenance
Phosphorus
Aluminum
Serum
Bicarbonates
Parathyroid Hormone
Leukocyte Count
Control Groups
Urea
ferric citrate
Nitrogen
Lymphocytes
Inflammation
Calcium
Hyperphosphatemia

Keywords

  • adverse events
  • calcium acetate
  • end-stage renal disease (ESRD)
  • ferric citrate
  • hyperphosphatemia
  • Index Words Hemodialysis
  • mineral bone disease
  • phosphate binder
  • protein-energy wasting (PEW)/inflammation
  • safety
  • sevelamer carbonate

ASJC Scopus subject areas

  • Nephrology

Cite this

The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients : Results from Prespecified Analyses of a Randomized Clinical Trial. / Van Buren, Peter N.; Lewis, Julia B.; Dwyer, Jamie P.; Greene, Tom; Middleton, John; Sika, Mohammed; Umanath, Kausik; Abraham, Josephine D.; Arfeen, Shahabul S.; Bowline, Isai G.; Chernin, Gil; Fadem, Stephen Z.; Goral, Simin; Koury, Mark; Sinsakul, Marvin V.; Weiner, Daniel E.

In: American Journal of Kidney Diseases, Vol. 66, No. 3, 01.09.2015, p. 479-488.

Research output: Contribution to journalArticle

Van Buren, PN, Lewis, JB, Dwyer, JP, Greene, T, Middleton, J, Sika, M, Umanath, K, Abraham, JD, Arfeen, SS, Bowline, IG, Chernin, G, Fadem, SZ, Goral, S, Koury, M, Sinsakul, MV & Weiner, DE 2015, 'The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results from Prespecified Analyses of a Randomized Clinical Trial', American Journal of Kidney Diseases, vol. 66, no. 3, pp. 479-488. https://doi.org/10.1053/j.ajkd.2015.03.013
Van Buren, Peter N. ; Lewis, Julia B. ; Dwyer, Jamie P. ; Greene, Tom ; Middleton, John ; Sika, Mohammed ; Umanath, Kausik ; Abraham, Josephine D. ; Arfeen, Shahabul S. ; Bowline, Isai G. ; Chernin, Gil ; Fadem, Stephen Z. ; Goral, Simin ; Koury, Mark ; Sinsakul, Marvin V. ; Weiner, Daniel E. / The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients : Results from Prespecified Analyses of a Randomized Clinical Trial. In: American Journal of Kidney Diseases. 2015 ; Vol. 66, No. 3. pp. 479-488.
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abstract = "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.",
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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.

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.

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KW - hyperphosphatemia

KW - Index Words Hemodialysis

KW - mineral bone disease

KW - phosphate binder

KW - protein-energy wasting (PEW)/inflammation

KW - safety

KW - sevelamer carbonate

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