title: Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials.
abstract: BACKGROUND
  Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD.
  
  
  METHODS
  Network meta-analysis.
  
  
  METHODS
  Adults with CKD.
  
  
  METHODS
  Randomized trials with allocation to phosphate binders.
  
  
  METHODS
  Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium.
  
  
  RESULTS
  The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification.
  
  
  RESULTS
  77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium.
  
  
  CONCLUSIONS
  Limited testing of consistency; short follow-up.
  
  
  CONCLUSIONS
  There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials.
authors.affiliation: Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.affiliation: Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Sharon
authors.initials: S
authors.lastname: Gardner
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina, Greece; Department of Primary Education, University of Ioannina, Ioannina, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavridis
authors.affiliation: Division of Medicine, Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Sydney School of Public Health, The University of Sydney, NSW, Australia.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Whangarei Hospital, Whangarei, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: French
authors.affiliation: Division of Nephrology and Transplantation, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; Diaverum Medical Scientific Office, Diaverum Sweden AB, Lund, Sweden.
authors.forename: Marinella
authors.initials: M
authors.lastname: Ruospo
authors.affiliation: Sydney School of Public Health, The University of Sydney, NSW, Australia; Diaverum Medical Scientific Office, Diaverum Sweden AB, Lund, Sweden; Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. Electronic address: gfmstrippoli@gmail.com.
authors.forename: Giovanni F M
authors.initials: GF
authors.lastname: Strippoli
mesh_terms: D000328:Adult; D002614:Chelating Agents / Q000627:therapeutic use*; D006801:Humans; D007811:Lanthanum / Q000627:therapeutic use; D010710:Phosphates; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D000069603:Sevelamer / Q000627:therapeutic use
chemical_list: D002614:Chelating Agents; D010710:Phosphates; C119467:lanthanum carbonate; D007811:Lanthanum; D000069603:Sevelamer
keywords: Phosphate-binding agents; calcium; chronic kidney disease (CKD); iron; lanthanum; meta-analysis; mortality; phosphate binder; sevelamer