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Phosphate binders for preventing and treating bone disease in chronic kidney disease patients

Abstract

BACKGROUND: Phosphate binders are widely used to lower serum phosphorus levels in people with chronic kidney disease (CKD) but their impact in CKD remains controversial. OBJECTIVES: To review the effects of various phosphate binders on biochemical and patient-level end-points in CKD stages 3 to 5D. SEARCH STRATEGY: In March 2010 we searched MEDLINE, EMBASE, the Cochrane Renal Group's Specialised Register and CENTRAL for relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of various phosphate binders in adults with CKD. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed search results and extracted data. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using a random-effects model. MAIN RESULTS: Sixty studies (7631 participants) were included. There was no significant reduction in all-cause mortality (10 studies, 3079 participants: RR 0.73, 95% CI 0.46 to 1.16), or serum calcium by phosphorus (Ca x P) product with sevelamer hydrochloride compared to calcium-based agents. There was a significant reduction in serum phosphorus (16 studies, 3126 participants: MD 0.23 mg/dL, 95% CI 0.04 to 0.42) and parathyroid hormone (PTH) (12 studies, 2551 participants; MD 56 pg/mL, 95% CI 26 to 84) but a significant increase in the risk of hypercalcaemia (12 studies, 1144 participants: RR 0.45, 95% CI 0.35 to 0.59) with calcium-based agents compared to sevelamer hydrochloride. There was a significant increase in the risk of adverse gastrointestinal events with sevelamer hydrochloride in comparison to calcium salts (5 studies, 498 participants: RR 1.58, 95% CI 1.11 to 2.25). Compared with calcium-based agents, lanthanum significantly reduced serum calcium (2 studies, 122 participants: MD -0.30 mg/dL, 95% CI -0.64 to -0.25) and the Ca x P product, but not serum phosphorus levels. The effects of calcium acetate on biochemical end-points were similar to those of calcium carbonate. The phosphorus lowering effects of novel agents such as ferric citrate, colestilan and niacinamide were only reported in a few studies. AUTHORS' CONCLUSIONS: Available phosphate-binding agents have been shown to reduce phosphorus levels in comparison to placebo. However, there are insufficient data to establish the comparative superiority of novel non-calcium binding agents over calcium-containing phosphate binders for patient-level outcomes such as all-cause mortality and cardiovascular end-points in CKD.

Type Journal
ISBN 1469-493X (Electronic) 1361-6137 (Linking)
Authors Navaneethan, S. D.; Palmer, S. C.; Vecchio, M.; Craig, J. C.; Elder, G. J.; Strippoli, G. F.;
Publisher Name COCHRANE DB SYST REV
Published Date 2011-01-01 00:00:00
Published Issue 2
Published Pages CD006023
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21328279
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11299_11738/11 Navaneethan CD006023.pdf