Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis

• Published in: PloS one 2016-06, Vol.11 (6), p.e0156891-e0156891
• Main Authors: Sekercioglu, Nigar, Thabane, Lehana, Díaz Martínez, Juan Pablo, Nesrallah, Gihad, Longo, Christopher J, Busse, Jason W, Akhtar-Danesh, Noori, Agarwal, Arnav, Al-Khalifah, Reem, Iorio, Alfonso, Guyatt, Gordon H
• Format: Article
• Language: English
• Subjects: Acetic acid; Binders; Biology and Life Sciences; Bone diseases; Calcification; Calcium; Calcium acetate; Calcium carbonate; Calcium phosphates; Cardiovascular diseases; Care and treatment; Chelating Agents - therapeutic use; Chronic kidney failure; Citric acid; Clinical trials; Clinical Trials, Phase IV as Topic; Collection Review; Comparative analysis; Confidence intervals; Dietary restrictions; Dosage and administration; Epidemiology; Ethics; Evaluation; Female; Ferric citrate; Hemodialysis; Hospitalization; Humans; Iron; Kidney diseases; Kidneys; Lanthanum; Male; Medicine; Medicine and Health Sciences; Meta-analysis; Metabolism; Mineralization; Minerals; Mortality; Nutrient deficiency; Patient outcomes; Patients; Pediatrics; People and Places; Phosphate; Phosphate binders; Phosphates; Phosphates - blood; Phosphorus; Physical Sciences; Prospero protein; Randomization; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - drug therapy; Research and Analysis Methods; Risk assessment; Risk factors; Smooth muscle; Studies; Systematic review; Transplants & implants; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156891

Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no d