Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial.

Abstract

BACKGROUND AND OBJECTIVES:

Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

We conducted a randomized controlled trial of prevalent hemodialysis recipients already receiving calcium carbonate as a phosphate binder at five Canadian centers between March 31, 2014 and October 2, 2014. Participants were randomly allocated to 26 weeks of an intensive phosphate goal of 2.33-4.66 mg/dl (0.75-1.50 mmol/L) or a liberalized target of 6.20-7.75 mg/dl (2.00-2.50 mmol/L) by titrating calcium carbonate using a dosing nomogram. The primary outcome was the difference in the change in serum phosphate from randomization to 26 weeks.

RESULTS:

Fifty-three participants were randomized to the intensive group and 51 to the liberalized group. The median (interquartile range) daily dose of elemental calcium at 26 weeks was 1800 (1275-3000) mg in the intensive group, and 0 (0-500) mg in the liberalized group. The mean (SD) serum phosphate at 26 weeks was 4.53 (1.12) mg/dl (1.46 [0.36] mmol/L) in the intensive group and 6.05 (1.40) mg/dl (1.95 [0.45] mmol/L) in the liberalized group. Phosphate concentration in the intensive group declined by 1.24 (95% confidence interval, 0.75 to 1.74) mg/dl (0.40 [95% confidence interval, 0.24 to 0.56] mmol/L) compared with the liberalized group. There were no statistically significant differences between the two groups in the risk of hypercalcemia, hypocalcemia, parathyroidectomy, or major vascular events.

CONCLUSIONS:

It is feasible to achieve and maintain a difference in serum phosphate concentrations in hemodialysis recipients by titrating calcium carbonate. A large trial is needed to determine if targeting a lower serum phosphate concentration improves patient-important outcomes.

• Authors: Ron Wald, Christian G Rabbat, Louis Girard, Amit X Garg, Karthik Tennankore, Jessica Tyrwhitt, Andrew Smyth, Andrea Rathe-Skafel, Peggy Gao, Andrea Mazzetti, Jackie Bosch, Andrew T Yan, Patrick Parfrey, Braden J Manns, Michael Walsh
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 12 Issue 6 Pg. 965-973 (Jun 07 2017) ISSN: 1555-905X [Electronic] United States
• PMID: 28550080 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2017 by the American Society of Nephrology.

Chemical References

• Biomarkers
• Chelating Agents
• Phosphates
• Calcium Carbonate

Topics

• Aged
• Biomarkers (blood)
• Calcium Carbonate (administration & dosage, adverse effects)
• Canada
• Chelating Agents (administration & dosage, adverse effects)
• Drug Dosage Calculations
• Drug Monitoring
• Feasibility Studies
• Female
• Humans
• Hyperphosphatemia (blood, etiology, prevention & control)
• Kidney Failure, Chronic (blood, diagnosis, therapy)
• Male
• Middle Aged
• Nomograms
• Phosphates (blood)
• Pilot Projects
• Quality of Life
• Renal Dialysis (adverse effects)
• Time Factors
• Treatment Outcome