Benefits and Harms of Phosphate Binders in CKD: A Systematic Review of Randomized Controlled Trials

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.

Index Words: Phosphate binders, hyperphosphatemia, bone disease, calcification, chronic kidney disease