Benefits and Harms of Phosphate Binders in CKD: A Systematic Review of Randomized Controlled Trials
Received 13 February 2009; accepted 5 June 2009. published online 19 August 2009.
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.
A list of author affiliations appears at the end of this article
Address correspondence to Sankar D. Navaneethan, MD, MPH, Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Ave, Q7, Cleveland, OH 44122
Giovanni F.M. Strippoli, MD, PhD, MPH, MM, Department of Pharmacology and Clinical Epidemiology, Renal Division, Mario Negri Sud Consortium, S Maria Imbaro (Ch), Italy
This review is excerpted from a Cochrane Review to be published in The Cochrane Library (http://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/HOME). Cochrane Reviews are regularly updated as new evidence emerges in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review.
ABSTRACT