FINAL Use of phosphate binders Chronic kidney disease: evidence reviews for the use of phosphate binders FINAL (August 2021) 642 Pairwise analysis Adults with stage 4 or 5 CKD who are not on dialysis Calcium acetate vs Placebo Quality assessment No of patients Effect Quality No of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Calcium acetate Placebo Relative (95% CI) Absolute Serum Phosphate (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.22] 1 1 randomised trials serious 2 no serious inconsistency no serious indirectness serious 3 none 37 41 - MD 0.23 lower (0.42 to 0.04 lower) LOW Proportion achieving phosphate control 1 1 randomised trials serious 2 no serious inconsistency no serious indirectness serious 3 none 22/37 (59.5%) 36.6% RR 1.63 (1 to 2.63) 23 more per 100 (from 0 more to 60 more) LOW Serum Calcium (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.10] 1 1 randomised trials serious 2 no serious inconsistency no serious indirectness serious 3 none 37 41 - MD 0.17 higher (0.08 to 0.26 higher) LOW Risk of hypercalcaemia
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FINAL Use of phosphate binders
Chronic kidney disease: evidence reviews for the use of phosphate binders FINAL (August 2021)
642
Pairwise analysis
Adults with stage 4 or 5 CKD who are not on dialysis Calcium acetate vs Placebo
Quality assessment No of patients Effect
Quality
No of studies
Design Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Calcium acetate
Placebo Relative (95% CI)
Absolute
Serum Phosphate (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.22]
11 randomised trials
serious2 no serious inconsistency
no serious indirectness
serious3 none 37 41 - MD 0.23 lower (0.42 to 0.04
lower)
LOW
Proportion achieving phosphate control
11 randomised trials
serious2 no serious inconsistency
no serious indirectness
serious3 none 22/37 (59.5%)
36.6% RR 1.63 (1 to 2.63)
23 more per 100 (from 0 more to 60
more)
LOW
Serum Calcium (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.10]
1 Qunibi 2011 2 Study at moderate or high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses both ends of a defined MID interval 5 95% confidence interval crosses line of no effect Calcium carbonate vs Lanthanum carbonate
Quality assessment No of patients Effect
Quality
No of studies
Design Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Calcium carbonate
Lanthanum carbonate
Relative (95% CI)
Absolute
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Serum Phosphate (mmol/L) at 4 months (Better indicated by lower values) [MID +/- 0.06]
1 Soriano 2013 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses both ends of a defined MID interval Lanthanum carbonate vs Placebo
Quality assessment No of patients Effect
Quality
No of studies
Design Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Lanthanum carbonate
Placebo Relative (95% CI)
Absolute
Serum Phosphate (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.15]
1 Sprague 2009; Takahara 2014 2 >33.3% of weighted data from studies at high risk of bias 3 i-squared >66.7% 4 95% confidence interval crosses one end of a defined MID interval 5 i-squared >33.3% 6 Sprague 2009 7 Study at high risk of bias 8 Takahara 2014 9 Study at moderate risk of bias 10 95% confidence interval crosses both ends of a defined MID interval Sevelamer hydrochloride vs Calcium acetate
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Quality assessment No of patients Effect
Quality No of
studies Design
Risk of bias
Inconsistency Indirectness Imprecision Other
considerations Sevelamer
hydrochloride Calcium acetate
Relative (95% CI)
Absolute
Serum Phosphate (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.11]
Serum Calcium (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.03]
1 randomised trials
very serious2
no serious inconsistency
no serious indirectness
serious4 none 25 25 - MD 0.07 lower (0.12 to 0.02
lower)
VERY LOW
1 Yilmaz 2012 2 Study at high risk of bias 3 95% confidence interval crosses both ends of a defined MID interval 4 95% confidence interval crosses one end of a defined MID interval Ferric citrate vs Placebo
Quality assessment No of patients Effect
Quality
No of studies
Design Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Ferric citrate
Placebo Relative (95% CI)
Absolute
Serum Phosphate (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.14]
11 randomised trials
very serious2
no serious inconsistency
no serious indirectness
no serious imprecision
none 57 29 - MD 0.41 lower (0.56 to 0.26
lower)
LOW
FINAL Use of phosphate binders
Chronic kidney disease: evidence reviews for the use of phosphate binders FINAL (August 2021)
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Proportion achieving phosphate control
11 randomised trials
very serious2
no serious inconsistency
no serious indirectness
no serious imprecision
none 37/57 (64.9%)
6.9% RR 9.41 (2.44 to 36.34)
58 more per 100 (from 10 more to
100 more)
LOW
Serum Calcium (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.05]
Chronic kidney disease: evidence reviews for the use of phosphate binders FINAL (August 2021)
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11 randomised trials
very serious2
no serious inconsistency
no serious indirectness
very serious5 none 6/60 (10%)
3.3% RR 3 (0.38 to 23.8)
7 more per 100 (from 2 fewer to
75 more)
VERY LOW
1 Yokoyama 2014a 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses line of no effect 5 95% confidence interval crosses both ends of a defined MID interval Calcium carbonate + low phosphate diet vs Low phosphate diet
Quality assessment No of patients Effect
Quality
No of studies
Design Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Calcium carbonate +
low phosphate diet
Low phosphate
diet
Relative (95% CI)
Absolute
Serum Phosphate (mmol/L) at 24 months (Better indicated by lower values) [MID +/- 0.14]
1 Russo 2007 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses both ends of a defined MID interval 5 95% confidence interval crosses line of no effect Sevelamer hydrochloride + low phosphate diet vs Low phosphate diet
Quality assessment No of patients Effect
Quality
No of studies
Design Risk of
bias Inconsistency Indirectness Imprecision
Other considerations
Sevelamer hydrochloride + low phosphate
diet
Low phosphate
diet
Relative (95% CI)
Absolute
Serum Phosphate (mmol/L) at 24 months (Better indicated by lower values) [MID +/- 0.14]
1 Russo 2007 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses line of no effect
Children and young people with stage 5 CKD who are on dialysis
Chronic kidney disease: evidence reviews for the use of phosphate binders FINAL (August 2021)
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1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious3 none 41 8 - MD 0.01 higher (0.15 lower to 0.17
higher)
LOW
Proportion with hypercalcaemia (Participants who developed ≥1 episode of sustained hypercalcemia [elevated serum calcium confirmed by repeat sample 1 week later] after start of treatment)
1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
no serious imprecision
none 4/66 (6.1%)
4/19 (21.1%)
RR 0.28 (0.08 to 1.04)
15 fewer per 100 (from 19
fewer to 1 more)
MODERATE
Adverse events: Constipation
1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious3 none 3/66 (4.5%)
1/19 (5.3%)
RR 0.86 (0.1 to 7.83)
1 fewer per 100 (from 5 fewer to 36
more)
LOW
Adverse events: Diarrhoea
1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious3 none 11/66 (16.7%)
0/19 (0%)
RR 6.87 (0.42 to 111.45)
- LOW
Adverse events: Nausea or vomiting
1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious3 none 8/66 (12.1%)
3/19 (15.8%)
RR 0.77 (0.23 to 2.61)
4 fewer per 100 (from 12 fewer to 25
more)
LOW
Discontinuation due to adverse events
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1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious3 none 12/66 (18.2%)
6/19 (31.6%)
RR 0.58 (0.25 to 1.33)
13 fewer per 100 (from 24 fewer to 10
more)
LOW
Adherence – mean percentage of adherence (Better indicated by higher values) [MID +/-19.0]
1 randomised trials1
no serious risk of bias
no serious inconsistency
no serious indirectness
serious2 none 66 19 - MD 17.30 higher (0.68
lower to 35.28 higher)
MODERATE
1 Greenbaum 2020 2 95% confidence interval crosses one end of a defined MID interval 3 95% confidence interval crosses both ends of a defined MID interval