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Meta-Analysis
. 2018 Aug 22;8(8):CD006023.
doi: 10.1002/14651858.CD006023.pub3.

Phosphate Binders for Preventing and Treating Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Affiliations
Free PMC article
Meta-Analysis

Phosphate Binders for Preventing and Treating Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Marinella Ruospo et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011.

Objectives: The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23.

Data collection and analysis: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes.

Main results: We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses.

Authors' conclusions: In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.

Conflict of interest statement

Nothing to declare

Figures

Figure 1
Figure 1
Flow diagram.
Figure 2
Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Analysis 1.1
Analysis 1.1
Comparison 1 Sevelamer versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 1.2
Analysis 1.2
Comparison 1 Sevelamer versus placebo or usual care, Outcome 2 Myocardial infarction.
Analysis 1.3
Analysis 1.3
Comparison 1 Sevelamer versus placebo or usual care, Outcome 3 Stroke.
Analysis 1.4
Analysis 1.4
Comparison 1 Sevelamer versus placebo or usual care, Outcome 4 Hospitalisation.
Analysis 1.5
Analysis 1.5
Comparison 1 Sevelamer versus placebo or usual care, Outcome 5 Fracture.
Analysis 1.6
Analysis 1.6
Comparison 1 Sevelamer versus placebo or usual care, Outcome 6 Pruritus.
Analysis 1.7
Analysis 1.7
Comparison 1 Sevelamer versus placebo or usual care, Outcome 7 Nausea.
Analysis 1.8
Analysis 1.8
Comparison 1 Sevelamer versus placebo or usual care, Outcome 8 Vomiting.
Analysis 1.9
Analysis 1.9
Comparison 1 Sevelamer versus placebo or usual care, Outcome 9 Abdominal pain.
Analysis 1.10
Analysis 1.10
Comparison 1 Sevelamer versus placebo or usual care, Outcome 10 Constipation.
Analysis 1.11
Analysis 1.11
Comparison 1 Sevelamer versus placebo or usual care, Outcome 11 Diarrhoea.
Analysis 1.12
Analysis 1.12
Comparison 1 Sevelamer versus placebo or usual care, Outcome 12 Abdominal bloating.
Analysis 1.13
Analysis 1.13
Comparison 1 Sevelamer versus placebo or usual care, Outcome 13 End‐stage kidney disease.
Analysis 1.14
Analysis 1.14
Comparison 1 Sevelamer versus placebo or usual care, Outcome 14 Coronary artery calcium score.
Analysis 1.15
Analysis 1.15
Comparison 1 Sevelamer versus placebo or usual care, Outcome 15 Serum phosphate.
Analysis 1.16
Analysis 1.16
Comparison 1 Sevelamer versus placebo or usual care, Outcome 16 Serum calcium.
Analysis 1.17
Analysis 1.17
Comparison 1 Sevelamer versus placebo or usual care, Outcome 17 Hypercalcaemia.
Analysis 1.18
Analysis 1.18
Comparison 1 Sevelamer versus placebo or usual care, Outcome 18 Serum calcium‐by‐phosphate product.
Analysis 1.19
Analysis 1.19
Comparison 1 Sevelamer versus placebo or usual care, Outcome 19 Serum iPTH.
Analysis 1.20
Analysis 1.20
Comparison 1 Sevelamer versus placebo or usual care, Outcome 20 Serum alkaline phosphatase.
Analysis 1.21
Analysis 1.21
Comparison 1 Sevelamer versus placebo or usual care, Outcome 21 Serum bicarbonate.
Analysis 1.22
Analysis 1.22
Comparison 1 Sevelamer versus placebo or usual care, Outcome 22 eGFR.
Analysis 1.23
Analysis 1.23
Comparison 1 Sevelamer versus placebo or usual care, Outcome 23 Bone mineral density: lumbar spine.
Analysis 1.24
Analysis 1.24
Comparison 1 Sevelamer versus placebo or usual care, Outcome 24 Bone mineral density: hip.
Analysis 1.25
Analysis 1.25
Comparison 1 Sevelamer versus placebo or usual care, Outcome 25 Klotho.
Analysis 2.1
Analysis 2.1
Comparison 2 Lanthanum versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 2.2
Analysis 2.2
Comparison 2 Lanthanum versus placebo or usual care, Outcome 2 Myocardial infarction.
Analysis 2.3
Analysis 2.3
Comparison 2 Lanthanum versus placebo or usual care, Outcome 3 Stroke.
Analysis 2.4
Analysis 2.4
Comparison 2 Lanthanum versus placebo or usual care, Outcome 4 Hospitalisation.
Analysis 2.5
Analysis 2.5
Comparison 2 Lanthanum versus placebo or usual care, Outcome 5 Fracture.
Analysis 2.6
Analysis 2.6
Comparison 2 Lanthanum versus placebo or usual care, Outcome 6 Pruritus.
Analysis 2.7
Analysis 2.7
Comparison 2 Lanthanum versus placebo or usual care, Outcome 7 Pruritus.
Analysis 2.8
Analysis 2.8
Comparison 2 Lanthanum versus placebo or usual care, Outcome 8 Nausea.
Analysis 2.9
Analysis 2.9
Comparison 2 Lanthanum versus placebo or usual care, Outcome 9 Vomiting.
Analysis 2.10
Analysis 2.10
Comparison 2 Lanthanum versus placebo or usual care, Outcome 10 Abdominal pain.
Analysis 2.11
Analysis 2.11
Comparison 2 Lanthanum versus placebo or usual care, Outcome 11 Constipation.
Analysis 2.12
Analysis 2.12
Comparison 2 Lanthanum versus placebo or usual care, Outcome 12 Diarrhoea.
Analysis 2.13
Analysis 2.13
Comparison 2 Lanthanum versus placebo or usual care, Outcome 13 End‐stage kidney disease.
Analysis 2.14
Analysis 2.14
Comparison 2 Lanthanum versus placebo or usual care, Outcome 14 Coronary artery calcification score.
Analysis 2.15
Analysis 2.15
Comparison 2 Lanthanum versus placebo or usual care, Outcome 15 Vascular calcification score.
Analysis 2.16
Analysis 2.16
Comparison 2 Lanthanum versus placebo or usual care, Outcome 16 Serum phosphate.
Analysis 2.17
Analysis 2.17
Comparison 2 Lanthanum versus placebo or usual care, Outcome 17 Serum calcium.
Analysis 2.18
Analysis 2.18
Comparison 2 Lanthanum versus placebo or usual care, Outcome 18 Hypercalcaemia.
Analysis 2.19
Analysis 2.19
Comparison 2 Lanthanum versus placebo or usual care, Outcome 19 Serum calcium‐by‐phosphate product.
Analysis 2.20
Analysis 2.20
Comparison 2 Lanthanum versus placebo or usual care, Outcome 20 Serum iPTH.
Analysis 2.21
Analysis 2.21
Comparison 2 Lanthanum versus placebo or usual care, Outcome 21 eGFR.
Analysis 2.22
Analysis 2.22
Comparison 2 Lanthanum versus placebo or usual care, Outcome 22 Bone mineral density: lumbar spine.
Analysis 2.23
Analysis 2.23
Comparison 2 Lanthanum versus placebo or usual care, Outcome 23 Serum FGF23.
Analysis 3.1
Analysis 3.1
Comparison 3 Iron versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 3.2
Analysis 3.2
Comparison 3 Iron versus placebo or usual care, Outcome 2 Fracture.
Analysis 3.3
Analysis 3.3
Comparison 3 Iron versus placebo or usual care, Outcome 3 Pruritus.
Analysis 3.4
Analysis 3.4
Comparison 3 Iron versus placebo or usual care, Outcome 4 Nausea.
Analysis 3.5
Analysis 3.5
Comparison 3 Iron versus placebo or usual care, Outcome 5 Constipation.
Analysis 3.6
Analysis 3.6
Comparison 3 Iron versus placebo or usual care, Outcome 6 Diarrhoea.
Analysis 3.7
Analysis 3.7
Comparison 3 Iron versus placebo or usual care, Outcome 7 Abdominal pain.
Analysis 3.8
Analysis 3.8
Comparison 3 Iron versus placebo or usual care, Outcome 8 Serum phosphate.
Analysis 3.9
Analysis 3.9
Comparison 3 Iron versus placebo or usual care, Outcome 9 Serum calcium.
Analysis 3.10
Analysis 3.10
Comparison 3 Iron versus placebo or usual care, Outcome 10 Serum calcium‐by‐phosphate product.
Analysis 3.11
Analysis 3.11
Comparison 3 Iron versus placebo or usual care, Outcome 11 Serum alkaline phosphatase.
Analysis 3.12
Analysis 3.12
Comparison 3 Iron versus placebo or usual care, Outcome 12 Serum bicarbonate.
Analysis 3.13
Analysis 3.13
Comparison 3 Iron versus placebo or usual care, Outcome 13 eGFR.
Analysis 4.1
Analysis 4.1
Comparison 4 Calcium versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 4.2
Analysis 4.2
Comparison 4 Calcium versus placebo or usual care, Outcome 2 Myocardial infarction.
Analysis 4.3
Analysis 4.3
Comparison 4 Calcium versus placebo or usual care, Outcome 3 Stroke.
Analysis 4.4
Analysis 4.4
Comparison 4 Calcium versus placebo or usual care, Outcome 4 Fracture.
Analysis 4.5
Analysis 4.5
Comparison 4 Calcium versus placebo or usual care, Outcome 5 Pruritus.
Analysis 4.6
Analysis 4.6
Comparison 4 Calcium versus placebo or usual care, Outcome 6 Nausea.
Analysis 4.7
Analysis 4.7
Comparison 4 Calcium versus placebo or usual care, Outcome 7 Vomiting.
Analysis 4.8
Analysis 4.8
Comparison 4 Calcium versus placebo or usual care, Outcome 8 Abdominal pain.
Analysis 4.9
Analysis 4.9
Comparison 4 Calcium versus placebo or usual care, Outcome 9 Constipation.
Analysis 4.10
Analysis 4.10
Comparison 4 Calcium versus placebo or usual care, Outcome 10 Diarrhoea.
Analysis 4.11
Analysis 4.11
Comparison 4 Calcium versus placebo or usual care, Outcome 11 Coronary artery calcification score.
Analysis 4.12
Analysis 4.12
Comparison 4 Calcium versus placebo or usual care, Outcome 12 Serum phosphate.
Analysis 4.13
Analysis 4.13
Comparison 4 Calcium versus placebo or usual care, Outcome 13 Serum calcium.
Analysis 4.14
Analysis 4.14
Comparison 4 Calcium versus placebo or usual care, Outcome 14 Hypercalcaemia.
Analysis 4.15
Analysis 4.15
Comparison 4 Calcium versus placebo or usual care, Outcome 15 Serum calcium‐by‐phosphate product.
Analysis 4.16
Analysis 4.16
Comparison 4 Calcium versus placebo or usual care, Outcome 16 Serum iPTH.
Analysis 4.17
Analysis 4.17
Comparison 4 Calcium versus placebo or usual care, Outcome 17 Serum alkaline phosphatase.
Analysis 4.18
Analysis 4.18
Comparison 4 Calcium versus placebo or usual care, Outcome 18 Serum bicarbonate.
Analysis 4.19
Analysis 4.19
Comparison 4 Calcium versus placebo or usual care, Outcome 19 eGFR.
Analysis 5.1
Analysis 5.1
Comparison 5 Bixalomer versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 5.2
Analysis 5.2
Comparison 5 Bixalomer versus placebo or usual care, Outcome 2 End‐stage kidney disease.
Analysis 5.3
Analysis 5.3
Comparison 5 Bixalomer versus placebo or usual care, Outcome 3 Nausea.
Analysis 5.4
Analysis 5.4
Comparison 5 Bixalomer versus placebo or usual care, Outcome 4 Abdominal pain.
Analysis 5.5
Analysis 5.5
Comparison 5 Bixalomer versus placebo or usual care, Outcome 5 Constipation.
Analysis 5.6
Analysis 5.6
Comparison 5 Bixalomer versus placebo or usual care, Outcome 6 Diarrhoea.
Analysis 6.1
Analysis 6.1
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 6.2
Analysis 6.2
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 2 Pruritus.
Analysis 6.3
Analysis 6.3
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 3 Constipation.
Analysis 6.4
Analysis 6.4
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 4 Diarrhoea.
Analysis 6.5
Analysis 6.5
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 5 Serum phosphate.
Analysis 6.6
Analysis 6.6
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 6 Serum calcium.
Analysis 6.7
Analysis 6.7
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 7 Serum iPTH.
Analysis 6.8
Analysis 6.8
Comparison 6 Nicotinamide versus placebo or usual care, Outcome 8 Serum calcium‐by‐phosphate product.
Analysis 7.1
Analysis 7.1
Comparison 7 Colestilan versus placebo or usual care, Outcome 1 Death (all causes).
Analysis 7.2
Analysis 7.2
Comparison 7 Colestilan versus placebo or usual care, Outcome 2 Nausea.
Analysis 7.3
Analysis 7.3
Comparison 7 Colestilan versus placebo or usual care, Outcome 3 Abdominal pain.
Analysis 7.4
Analysis 7.4
Comparison 7 Colestilan versus placebo or usual care, Outcome 4 Diarrhoea.
Analysis 7.5
Analysis 7.5
Comparison 7 Colestilan versus placebo or usual care, Outcome 5 Constipation.
Analysis 8.1
Analysis 8.1
Comparison 8 Sevelamer versus calcium, Outcome 1 Death (all causes).
Analysis 8.2
Analysis 8.2
Comparison 8 Sevelamer versus calcium, Outcome 2 Cardiovascular death.
Analysis 8.3
Analysis 8.3
Comparison 8 Sevelamer versus calcium, Outcome 3 Myocardial infarction.
Analysis 8.4
Analysis 8.4
Comparison 8 Sevelamer versus calcium, Outcome 4 Stroke.
Analysis 8.5
Analysis 8.5
Comparison 8 Sevelamer versus calcium, Outcome 5 Hospitalisation.
Analysis 8.6
Analysis 8.6
Comparison 8 Sevelamer versus calcium, Outcome 6 Fracture.
Analysis 8.7
Analysis 8.7
Comparison 8 Sevelamer versus calcium, Outcome 7 Nausea.
Analysis 8.8
Analysis 8.8
Comparison 8 Sevelamer versus calcium, Outcome 8 Vomiting.
Analysis 8.9
Analysis 8.9
Comparison 8 Sevelamer versus calcium, Outcome 9 Abdominal pain.
Analysis 8.10
Analysis 8.10
Comparison 8 Sevelamer versus calcium, Outcome 10 Constipation.
Analysis 8.11
Analysis 8.11
Comparison 8 Sevelamer versus calcium, Outcome 11 Diarrhoea.
Analysis 8.12
Analysis 8.12
Comparison 8 Sevelamer versus calcium, Outcome 12 Abdominal bloating.
Analysis 8.13
Analysis 8.13
Comparison 8 Sevelamer versus calcium, Outcome 13 Hypercalcaemia.
Analysis 8.14
Analysis 8.14
Comparison 8 Sevelamer versus calcium, Outcome 14 Calciphylaxis.
Analysis 8.15
Analysis 8.15
Comparison 8 Sevelamer versus calcium, Outcome 15 Coronary artery calcium score.
Analysis 8.16
Analysis 8.16
Comparison 8 Sevelamer versus calcium, Outcome 16 Serum phosphate.
Analysis 8.17
Analysis 8.17
Comparison 8 Sevelamer versus calcium, Outcome 17 Serum calcium.
Analysis 8.18
Analysis 8.18
Comparison 8 Sevelamer versus calcium, Outcome 18 Serum calcium‐by‐phosphate product.
Analysis 8.19
Analysis 8.19
Comparison 8 Sevelamer versus calcium, Outcome 19 Serum iPTH.
Analysis 8.20
Analysis 8.20
Comparison 8 Sevelamer versus calcium, Outcome 20 Serum alkaline phosphatase.
Analysis 8.21
Analysis 8.21
Comparison 8 Sevelamer versus calcium, Outcome 21 Serum bicarbonate.
Analysis 8.22
Analysis 8.22
Comparison 8 Sevelamer versus calcium, Outcome 22 eGFR.
Analysis 8.23
Analysis 8.23
Comparison 8 Sevelamer versus calcium, Outcome 23 Serum FGF23.
Analysis 8.24
Analysis 8.24
Comparison 8 Sevelamer versus calcium, Outcome 24 Soluble Klotho.
Analysis 9.1
Analysis 9.1
Comparison 9 Lanthanum versus calcium, Outcome 1 Death (all causes).
Analysis 9.2
Analysis 9.2
Comparison 9 Lanthanum versus calcium, Outcome 2 Hospitalisation.
Analysis 9.3
Analysis 9.3
Comparison 9 Lanthanum versus calcium, Outcome 3 Fracture.
Analysis 9.4
Analysis 9.4
Comparison 9 Lanthanum versus calcium, Outcome 4 Pruritus.
Analysis 9.5
Analysis 9.5
Comparison 9 Lanthanum versus calcium, Outcome 5 Nausea.
Analysis 9.6
Analysis 9.6
Comparison 9 Lanthanum versus calcium, Outcome 6 Vomiting.
Analysis 9.7
Analysis 9.7
Comparison 9 Lanthanum versus calcium, Outcome 7 Abdominal pain.
Analysis 9.8
Analysis 9.8
Comparison 9 Lanthanum versus calcium, Outcome 8 Constipation.
Analysis 9.9
Analysis 9.9
Comparison 9 Lanthanum versus calcium, Outcome 9 Diarrhoea.
Analysis 9.10
Analysis 9.10
Comparison 9 Lanthanum versus calcium, Outcome 10 Abdominal bloating.
Analysis 9.11
Analysis 9.11
Comparison 9 Lanthanum versus calcium, Outcome 11 Coronary artery calcium score.
Analysis 9.12
Analysis 9.12
Comparison 9 Lanthanum versus calcium, Outcome 12 Hypercalcaemia.
Analysis 9.13
Analysis 9.13
Comparison 9 Lanthanum versus calcium, Outcome 13 Serum phosphate.
Analysis 9.14
Analysis 9.14
Comparison 9 Lanthanum versus calcium, Outcome 14 Serum calcium.
Analysis 9.15
Analysis 9.15
Comparison 9 Lanthanum versus calcium, Outcome 15 Serum calcium‐by‐phosphate product.
Analysis 9.16
Analysis 9.16
Comparison 9 Lanthanum versus calcium, Outcome 16 Serum iPTH.
Analysis 9.17
Analysis 9.17
Comparison 9 Lanthanum versus calcium, Outcome 17 Serum alkaline phosphatase.
Analysis 9.18
Analysis 9.18
Comparison 9 Lanthanum versus calcium, Outcome 18 eGFR.
Analysis 9.19
Analysis 9.19
Comparison 9 Lanthanum versus calcium, Outcome 19 Serum FGF23.
Analysis 10.1
Analysis 10.1
Comparison 10 Magnesium versus calcium, Outcome 1 Hospitalisation.
Analysis 10.2
Analysis 10.2
Comparison 10 Magnesium versus calcium, Outcome 2 Constipation.
Analysis 10.3
Analysis 10.3
Comparison 10 Magnesium versus calcium, Outcome 3 Diarrhoea.
Analysis 11.1
Analysis 11.1
Comparison 11 Aluminium versus calcium, Outcome 1 Serum alkaline phosphatase.
Analysis 12.1
Analysis 12.1
Comparison 12 Magnesium plus calcium versus calcium, Outcome 1 Death (all causes).
Analysis 12.2
Analysis 12.2
Comparison 12 Magnesium plus calcium versus calcium, Outcome 2 Serum phosphate.
Analysis 12.3
Analysis 12.3
Comparison 12 Magnesium plus calcium versus calcium, Outcome 3 Serum calcium.
Analysis 12.4
Analysis 12.4
Comparison 12 Magnesium plus calcium versus calcium, Outcome 4 Serum calcium‐by‐phosphate product.
Analysis 12.5
Analysis 12.5
Comparison 12 Magnesium plus calcium versus calcium, Outcome 5 Serum iPTH.
Analysis 13.1
Analysis 13.1
Comparison 13 Sevelamer versus lanthanum, Outcome 1 Myocardial infarction.
Analysis 13.2
Analysis 13.2
Comparison 13 Sevelamer versus lanthanum, Outcome 2 Stroke.
Analysis 13.3
Analysis 13.3
Comparison 13 Sevelamer versus lanthanum, Outcome 3 Fracture.
Analysis 13.4
Analysis 13.4
Comparison 13 Sevelamer versus lanthanum, Outcome 4 Pruritus.
Analysis 13.5
Analysis 13.5
Comparison 13 Sevelamer versus lanthanum, Outcome 5 Nausea.
Analysis 13.6
Analysis 13.6
Comparison 13 Sevelamer versus lanthanum, Outcome 6 Vomiting.
Analysis 13.7
Analysis 13.7
Comparison 13 Sevelamer versus lanthanum, Outcome 7 Abdominal pain.
Analysis 13.8
Analysis 13.8
Comparison 13 Sevelamer versus lanthanum, Outcome 8 Constipation.
Analysis 13.9
Analysis 13.9
Comparison 13 Sevelamer versus lanthanum, Outcome 9 Diarrhoea.
Analysis 13.10
Analysis 13.10
Comparison 13 Sevelamer versus lanthanum, Outcome 10 Abdominal bloating.
Analysis 13.11
Analysis 13.11
Comparison 13 Sevelamer versus lanthanum, Outcome 11 Hypercalcaemia.
Analysis 14.1
Analysis 14.1
Comparison 14 Sevelamer versus iron, Outcome 1 Death (all causes).
Analysis 14.2
Analysis 14.2
Comparison 14 Sevelamer versus iron, Outcome 2 Cardiovascular death.
Analysis 14.3
Analysis 14.3
Comparison 14 Sevelamer versus iron, Outcome 3 Myocardial infarction.
Analysis 14.4
Analysis 14.4
Comparison 14 Sevelamer versus iron, Outcome 4 Fracture.
Analysis 14.5
Analysis 14.5
Comparison 14 Sevelamer versus iron, Outcome 5 Nausea.
Analysis 14.6
Analysis 14.6
Comparison 14 Sevelamer versus iron, Outcome 6 Abdominal pain.
Analysis 14.7
Analysis 14.7
Comparison 14 Sevelamer versus iron, Outcome 7 Constipation.
Analysis 14.8
Analysis 14.8
Comparison 14 Sevelamer versus iron, Outcome 8 Diarrhoea.
Analysis 14.9
Analysis 14.9
Comparison 14 Sevelamer versus iron, Outcome 9 Serum phosphate.
Analysis 14.10
Analysis 14.10
Comparison 14 Sevelamer versus iron, Outcome 10 Serum calcium.
Analysis 14.11
Analysis 14.11
Comparison 14 Sevelamer versus iron, Outcome 11 Serum bicarbonate.
Analysis 15.1
Analysis 15.1
Comparison 15 Sevelamer versus bixalomer, Outcome 1 Death (all causes).
Analysis 15.2
Analysis 15.2
Comparison 15 Sevelamer versus bixalomer, Outcome 2 Fracture.
Analysis 15.3
Analysis 15.3
Comparison 15 Sevelamer versus bixalomer, Outcome 3 Pruritus.
Analysis 15.4
Analysis 15.4
Comparison 15 Sevelamer versus bixalomer, Outcome 4 Nausea.
Analysis 15.5
Analysis 15.5
Comparison 15 Sevelamer versus bixalomer, Outcome 5 Vomiting.
Analysis 15.6
Analysis 15.6
Comparison 15 Sevelamer versus bixalomer, Outcome 6 Abdominal pain.
Analysis 15.7
Analysis 15.7
Comparison 15 Sevelamer versus bixalomer, Outcome 7 Constipation.
Analysis 15.8
Analysis 15.8
Comparison 15 Sevelamer versus bixalomer, Outcome 8 Abdominal bloating.
Analysis 15.9
Analysis 15.9
Comparison 15 Sevelamer versus bixalomer, Outcome 9 Serum phosphate.
Analysis 15.10
Analysis 15.10
Comparison 15 Sevelamer versus bixalomer, Outcome 10 Serum calcium.
Analysis 15.11
Analysis 15.11
Comparison 15 Sevelamer versus bixalomer, Outcome 11 Serum calcium‐by‐phosphate product.
Analysis 15.12
Analysis 15.12
Comparison 15 Sevelamer versus bixalomer, Outcome 12 Serum iPTH.
Analysis 15.13
Analysis 15.13
Comparison 15 Sevelamer versus bixalomer, Outcome 13 Serum bicarbonate.
Analysis 16.1
Analysis 16.1
Comparison 16 Sevelamer versus nicotinamide, Outcome 1 Death (all causes).
Analysis 16.2
Analysis 16.2
Comparison 16 Sevelamer versus nicotinamide, Outcome 2 Stroke.
Analysis 16.3
Analysis 16.3
Comparison 16 Sevelamer versus nicotinamide, Outcome 3 Vomiting.
Analysis 16.4
Analysis 16.4
Comparison 16 Sevelamer versus nicotinamide, Outcome 4 Serum calcium.
Analysis 16.5
Analysis 16.5
Comparison 16 Sevelamer versus nicotinamide, Outcome 5 Serum iPTH.
Analysis 16.6
Analysis 16.6
Comparison 16 Sevelamer versus nicotinamide, Outcome 6 Serum alkaline phosphatase.
Analysis 17.1
Analysis 17.1
Comparison 17 Sevelamer versus colestilan, Outcome 1 Death (all causes).
Analysis 17.2
Analysis 17.2
Comparison 17 Sevelamer versus colestilan, Outcome 2 Cardiovascular death.
Analysis 17.3
Analysis 17.3
Comparison 17 Sevelamer versus colestilan, Outcome 3 Myocardial infarction.
Analysis 17.4
Analysis 17.4
Comparison 17 Sevelamer versus colestilan, Outcome 4 Stroke.
Analysis 17.5
Analysis 17.5
Comparison 17 Sevelamer versus colestilan, Outcome 5 Pruritus.
Analysis 17.6
Analysis 17.6
Comparison 17 Sevelamer versus colestilan, Outcome 6 Nausea.
Analysis 17.7
Analysis 17.7
Comparison 17 Sevelamer versus colestilan, Outcome 7 Vomiting.
Analysis 17.8
Analysis 17.8
Comparison 17 Sevelamer versus colestilan, Outcome 8 Abdominal pain.
Analysis 17.9
Analysis 17.9
Comparison 17 Sevelamer versus colestilan, Outcome 9 Constipation.
Analysis 17.10
Analysis 17.10
Comparison 17 Sevelamer versus colestilan, Outcome 10 Diarrhoea.
Analysis 17.11
Analysis 17.11
Comparison 17 Sevelamer versus colestilan, Outcome 11 Serum phosphate.
Analysis 17.12
Analysis 17.12
Comparison 17 Sevelamer versus colestilan, Outcome 12 Serum calcium.
Analysis 17.13
Analysis 17.13
Comparison 17 Sevelamer versus colestilan, Outcome 13 Serum calcium‐by‐phosphate product.
Analysis 17.14
Analysis 17.14
Comparison 17 Sevelamer versus colestilan, Outcome 14 Serum iPTH.
Analysis 17.15
Analysis 17.15
Comparison 17 Sevelamer versus colestilan, Outcome 15 Serum alkaline phosphatase.
Analysis 18.1
Analysis 18.1
Comparison 18 Sevelamer versus aluminium, Outcome 1 Nausea.
Analysis 18.2
Analysis 18.2
Comparison 18 Sevelamer versus aluminium, Outcome 2 Constipation.
Analysis 18.3
Analysis 18.3
Comparison 18 Sevelamer versus aluminium, Outcome 3 Serum phosphate.
Analysis 18.4
Analysis 18.4
Comparison 18 Sevelamer versus aluminium, Outcome 4 Serum calcium.
Analysis 18.5
Analysis 18.5
Comparison 18 Sevelamer versus aluminium, Outcome 5 Serum iPTH.
Analysis 19.1
Analysis 19.1
Comparison 19 Sevelamer versus magnesium, Outcome 1 Serum phosphate.
Analysis 19.2
Analysis 19.2
Comparison 19 Sevelamer versus magnesium, Outcome 2 Serum calcium.
Analysis 19.3
Analysis 19.3
Comparison 19 Sevelamer versus magnesium, Outcome 3 Serum calcium‐by‐phosphate product.
Analysis 19.4
Analysis 19.4
Comparison 19 Sevelamer versus magnesium, Outcome 4 Serum iPTH.
Analysis 20.1
Analysis 20.1
Comparison 20 Sevelamer versus sevelamer + calcium, Outcome 1 Hypercalcaemia.
Analysis 20.2
Analysis 20.2
Comparison 20 Sevelamer versus sevelamer + calcium, Outcome 2 Serum calcium‐by‐phosphate product.
Analysis 21.1
Analysis 21.1
Comparison 21 Sevelamer versus calcium + magnesium, Outcome 1 Serum phosphate.
Analysis 21.2
Analysis 21.2
Comparison 21 Sevelamer versus calcium + magnesium, Outcome 2 Serum calcium.
Analysis 21.3
Analysis 21.3
Comparison 21 Sevelamer versus calcium + magnesium, Outcome 3 Serum iPTH.
Analysis 21.4
Analysis 21.4
Comparison 21 Sevelamer versus calcium + magnesium, Outcome 4 Serum alkaline phosphatase.
Analysis 21.5
Analysis 21.5
Comparison 21 Sevelamer versus calcium + magnesium, Outcome 5 Serum bicarbonate.
Analysis 22.1
Analysis 22.1
Comparison 22 Sevelamer hydrochloride versus sevelamer carbonate, Outcome 1 Death (all causes).
Analysis 22.2
Analysis 22.2
Comparison 22 Sevelamer hydrochloride versus sevelamer carbonate, Outcome 2 Nausea.
Analysis 22.3
Analysis 22.3
Comparison 22 Sevelamer hydrochloride versus sevelamer carbonate, Outcome 3 Vomiting.
Analysis 22.4
Analysis 22.4
Comparison 22 Sevelamer hydrochloride versus sevelamer carbonate, Outcome 4 Constipation.
Analysis 22.5
Analysis 22.5
Comparison 22 Sevelamer hydrochloride versus sevelamer carbonate, Outcome 5 Diarrhoea.
Analysis 23.1
Analysis 23.1
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 1 Death (all causes).
Analysis 23.2
Analysis 23.2
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 2 Hypercalcaemia.
Analysis 23.3
Analysis 23.3
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 3 Serum phosphate.
Analysis 23.4
Analysis 23.4
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 4 Serum calcium.
Analysis 23.5
Analysis 23.5
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 5 Serum calcium‐by‐phosphate product.
Analysis 23.6
Analysis 23.6
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 6 Serum iPTH.
Analysis 23.7
Analysis 23.7
Comparison 23 Calcium acetate versus calcium carbonate, Outcome 7 Serum alkaline phosphatase.
Analysis 24.1
Analysis 24.1
Comparison 24 Subgroup: sevelamer versus calcium, Outcome 1 Death (all causes): age.
Analysis 24.2
Analysis 24.2
Comparison 24 Subgroup: sevelamer versus calcium, Outcome 2 Death (all causes): CKD GFR category.
Analysis 24.3
Analysis 24.3
Comparison 24 Subgroup: sevelamer versus calcium, Outcome 3 Cardiovascular death: CKD GFR category.
Analysis 24.4
Analysis 24.4
Comparison 24 Subgroup: sevelamer versus calcium, Outcome 4 Death (all causes): study duration.
Analysis 24.5
Analysis 24.5
Comparison 24 Subgroup: sevelamer versus calcium, Outcome 5 Death (all causes): random sequence generation and allocation concealment.

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