title: 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.
  
  
  OBJECTIVE
  To review the effects of various phosphate binders on biochemical and patient-level end-points in CKD stages 3 to 5D.
  
  
  METHODS
  In March 2010 we searched MEDLINE, EMBASE, the Cochrane Renal Group's Specialised Register and CENTRAL for relevant studies.
  
  
  METHODS
  Randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of various phosphate binders in adults with CKD.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Nephrology and Hypertension, Glickman Urological and Kidney institute, Cleveland Clinic, Cleveland, OH, USA, 44195.
authors.forename: Sankar D
authors.initials: SD
authors.lastname: Navaneethan
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Vecchio
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Grahame J
authors.initials: GJ
authors.lastname: Elder
authors.forename: Giovanni Fm
authors.initials: GF
authors.lastname: Strippoli
mesh_terms: D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000517:prevention & control; D002118:Calcium / Q000097:blood; D017610:Calcium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D007674:Kidney Diseases / Q000097:blood / Q000150:complications*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood*; D011073:Polyamines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069603:Sevelamer
chemical_list: D017610:Calcium Compounds; D002614:Chelating Agents; D010281:Parathyroid Hormone; D011073:Polyamines; D010758:Phosphorus; D000069603:Sevelamer; D002118:Calcium