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2016 ; 11
(6
): e0156891
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Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney
Disease: A Systematic Review and Network Meta-Analysis
#MMPMID27276077
Sekercioglu N
; Thabane L
; Díaz Martínez JP
; Nesrallah G
; Longo CJ
; Busse JW
; Akhtar-Danesh N
; Agarwal A
; Al-Khalifah R
; Iorio A
; Guyatt GH
PLoS One
2016[]; 11
(6
): e0156891
PMID27276077
show ga
BACKGROUND: 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. METHODS: 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. RESULTS: 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 difference in cardiovascular mortality
between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence).
Our results suggest higher hospitalization, although non-significant, with
calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence).
DISCUSSION/CONCLUSIONS: Use of calcium results in higher mortality than either
sevelamer in particular and NCBPBs in general (moderate quality evidence). Our
results raise questions about whether administration of calcium as an
intervention for CKD- MBD remains ethical. Further research is needed to explore
the effects of different types of phosphate binders, including novel agents such
as iron, on quality and quantity of life. SYSTEMATIC REVIEW REGISTRATION:
PROSPERO CRD-42016032945.
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