Benefits and harms of phosphate binders in CKD: a systematic review of randomized controlled trials

Am J Kidney Dis. 2009 Oct;54(4):619-37. doi: 10.1053/j.ajkd.2009.06.004. Epub 2009 Aug 18.


Background: Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on biochemical and patient-level end points in patients with CKD.

Study design: Systematic review and meta-analysis by searching MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), and the Cochrane Renal Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL).

Setting & population: Patients with CKD.

Selection criteria for studies: Randomized controlled trials.

Intervention: Phosphate binders.

Outcomes: Serum phosphorus, calcium, and parathyroid hormone levels; incidence of hypercalcemia; all-cause mortality; adverse effects.

Results: 40 trials (6,406 patients) were included. There was no significant decrease in all-cause mortality (10 randomized controlled trials; 3,079 patients; relative risk [RR], 0.73; 95% confidence interval [CI], 0.46 to 1.16), hospitalization, or end-of-treatment serum calcium-phosphorus product levels with sevelamer compared with calcium-based agents. There was a significant decrease in end-of-treatment phosphorus and parathyroid hormone levels with calcium salts compared with sevelamer and a significant decrease in risk of hypercalcemia (RR, 0.47; 95% CI, 0.36 to 0.62) with sevelamer compared with calcium-based agents. There was a significant increase in risk of gastrointestinal adverse events with sevelamer in comparison to calcium salts (RR, 1.39; 95% CI, 1.04 to 1.87). Compared with calcium-based agents, lanthanum significantly decreased end-of-treatment serum calcium and calcium-phosphorus product levels, but with similar end-of-treatment phosphorus levels. Effects of calcium acetate on biochemical end points were similar to those of calcium carbonate. Existing data are insufficient to conclude for a differential impact of any phosphate binder on cardiovascular mortality or other patient-level outcome.

Limitations: Few long-term studies of the efficacy of phosphate binders on mortality and musculoskeletal morbidity, significant heterogeneity for many surrogate outcomes, and suboptimal reporting of study methods to determine trial quality.

Conclusion: Currently, there are insufficient data to establish the comparative superiority of non-calcium-binding agents over calcium-containing phosphate binders for such important patient-level outcomes as all-cause mortality and cardiovascular end points. Additional trials are still required to examine the differential effects of phosphate-binding agents on these end points and the mineral homeostasis pathway.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Acetates / therapeutic use
  • Biomarkers / blood
  • Bone Density Conservation Agents / therapeutic use
  • Calcium / blood
  • Calcium Carbonate / therapeutic use
  • Calcium Compounds / administration & dosage
  • Calcium Compounds / adverse effects
  • Calcium Compounds / therapeutic use*
  • Chelating Agents / therapeutic use
  • Chronic Kidney Disease-Mineral and Bone Disorder / blood
  • Chronic Kidney Disease-Mineral and Bone Disorder / complications
  • Chronic Kidney Disease-Mineral and Bone Disorder / etiology
  • Chronic Kidney Disease-Mineral and Bone Disorder / prevention & control
  • Humans
  • Hypercalcemia / chemically induced
  • Hyperphosphatemia / drug therapy*
  • Hyperphosphatemia / etiology
  • Lanthanum / therapeutic use*
  • Parathyroid Hormone / blood
  • Phosphates / metabolism*
  • Phosphorus / blood*
  • Polyamines / therapeutic use*
  • Randomized Controlled Trials as Topic / methods
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / mortality
  • Research Design
  • Sevelamer


  • Acetates
  • Biomarkers
  • Bone Density Conservation Agents
  • Calcium Compounds
  • Chelating Agents
  • Parathyroid Hormone
  • Phosphates
  • Polyamines
  • Phosphorus
  • lanthanum carbonate
  • Lanthanum
  • Sevelamer
  • Calcium Carbonate
  • Calcium
  • calcium acetate