The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a meta-analysis of randomized trials

Figures & data

Figure 1. Selection of studies.

Table 1. Characteristics of included studies.

Study	Country	No. of patients (NCPB/CPB)	Mean age (NCPB/CPB)	Drugs used (NCPB/CPB)	Primary outcomes
Barreto et al.18	Brazil	41/30	47 ± 13/47 ± 14	Sevelamer/CA	Coronary artery calcification; serum markers of mineral metabolism; bone biopsy.
Block et al.20	USA	54/55	57 ± 15/59 ± 15	Sevelamer/not mention which kind of CPB	Coronary artery calcification; serum markers of mineral metabolism.
Braun et al.21	Germany	55/59	55 ± 13/58 ± 15	Sevelamer/CC	Coronary artery calcification; serum markers of mineral metabolism.
Chertow et al.4	USA	99/101	57 ± 14/56 ± 16	Sevelamer/CC, CA	Coronary artery calcification; serum markers of mineral metabolism.
Evenepoel et al.19	Europe (including 7 countries)	97/46	54.6 ± 15.7/54.1 ± 15.8	Sevelamer/ CA	Serum markers of mineral metabolism.
Ferreira et al.23	Portugal	44/47	55.5 ± 15.4/53.9 ± 13.7	Sevelamer/CC	Serum markers of mineral metabolism; bone biopsy.
Freemont et al.24	UK	49/49	55.9 ± 13.5/54 ± 15.2	LC/CC	Serum markers of mineral metabolism; bone biopsy.
Kakuta et al.9	Japan	91/92	59 ± 12/57 ± 12	Sevelamer/CC	Coronary artery calcification; serum markers of mineral metabolism.
Kalil et al.22	USA	10/10	65 ± 9/68 ± 9	LC/CC	Coronary artery calcification; serum markers of mineral metabolism.
Lee et al.15	Korea	35/37	48.25 ± 11.06/ 51.80 ± 11.62	LC/CC	Serum markers of mineral metabolism.
Navarro-Gonzalez et al.	Spain	33/32	59.6 ± 16.9/ 62.8 ± 14.1	Sevelamer /CC	Serum markers of mineral metabolism; serum inflammatory profile.
Qunibi et al.10	USA	100/103	60.3 ± 12.1/58.5 ± 12.8	Sevelamer/ CA	Coronary artery calcification; serum markers of mineral metabolism.
Sadek et al.17	France	21/21	Unreported	Sevelamer /CC	Serum markers of mineral metabolism.
Spasovski et al.25	Macedonia	12/12	55 ± 10/ 57 ± 10	LC/CC	Bone biopsy.
Suki et al.28	USA	1053/1050	59.9 ± 14.3/ 60.1 ± 15.2	Sevelamer/CA, CC	All cause mortality; serum markers of mineral metabolism.
Toussaint et al.26	Australia	22/23	56 ± 15.2/ 58.8 ± 14.9	LC/CC	Coronary artery calcification; all cause mortality.
Wesseling-Perry et al.27	USA	28/23	13.9 ± 0.7 (all the patients)	Sevelamer/CC	Serum markers of mineral metabolism.
Takei et al.29	Japan	22/20	54.4 ± 9.8/ 54.2 ± 8.8	Sevelamer/CC	Serum markers of mineral metabolism.

Notes: NCPB: non-calcium-based phosphate binders; CPB: calcium-based phosphate binders; CA: Calcium acetate; CC: calcium carbonate; LC: lanthanum carbonate.

Table 2. Quality assessment of included studies.

Study	Randomization	Allocated concealment	Blinding	Length of follow-up	Withdrawal/Lost to follow-up (%)
Barreto et al.18	Adequate	Unclear	Unclear	12 months	19.8
Block et al.20	Adequate	Unclear	Unclear	18 months	18.3
Braun et al.21	Adequate	Unclear	Unclear	52 weeks	27.2
Chertow et al.4	Adequate	No	No	52 weeks	5.5
Evenepoel et al.	Adequate	Unclear	Unclear	12 weeks	27.3
Ferreira et al.23	Adequate	No	No	52 weeks	25.3
Freemont et al.24	Unclear	Unclear	Unclear	53 weeks	30.6
Kakuta et al.9	Adequate	Adequate	Adequate	12 months	1.1
Kalil et al.22	Adequate	Adequate	Adequate	12 months	35
Lee et al.15	Unclear	Unclear	Unclear	24 weeks	30.6
Navarro-Gonzalez et al.	Adequate	Unclear	Unclear	12 weeks	7.7
Qunibi et al.	Adequate	Unclear	Unclear	12 months	36.5
Sadek et al.17	Unclear	Unclear	Unclear	5 months	26.2
Spasovski et al.25	Unclear	Unclear	Unclear	2 years	20.8
Suki et al.	Unclear	No	No	48 months	10.7
Toussaint et al.26	Adequate	Unclear	Unclear	18 months	28.9
Wesseling-Perry et al.27	Unclear	Unclear	Unclear	8 months	31.7
Takei et al.29	Adequate	Unclear	Unclear	24 weeks	0

Figure 2. Forest plots of main effects of NCBP and CBP on CAC scores according to duration of follow-up. NCBP = non-calcium-based phosphate binders; CBP = calcium-based phosphate binders; WMD = weighted mean differences.

Figure 3. Forest plots of main effects of NCBP and CBP on cardiovascular events and all cause mortality. NCBP = non-calcium-based phosphate binders; CBP = calcium-based phosphate binders; RR = relative risks.

Table 3. Comparison of serum mineral metabolism markers changes between NCPB groups and CPB groups.

		Random-effects model		Fixed-effects model		Heterogeneity
Biochemical markers	No. of studies	WMD (95% CI)	p-Value	WMD (95% CI)	p-Value	p-Value	I^2, %
iPTH (pg/mL)	9	57.1 (13.42, 100.78)	0.01	41.62 (13.53, 69.70)	0.004	0.04	50
Calcium (mg/dL)	13	−0.26 (−0.37, −0.14)	<0.0001	−0.31 (−0.36, −0.27)	<0.0001	<0.0001	81
Phosphate (mg/dL)	12	0.06 (−0.09, 0.20)	0.46	0.07 (−0.02, 0.16)	0.14	0.09	38
Ca × P (mg^2/dL^2)	10	−0.45 (−2.17, 1.28)	0.61	−1.71 (−2.36, −1.07)	<0.0001	<0.0001	76
LDL-C (mg/dL)	9	−20.93 (−30.56, −11.3)	<0.0001	−17.23 (−20.29, −14.16)	<0.0001	<0.0001	89
HDL-C (mg/dL)	8	0.53 (−1.02, 2.09)	0.50	0.5 (−1.0, 1.99)	0.52	0.4	4
Pentosidine (nmol/mL)	1	−0.24 (−0.50, 0.02)	0.07	−0.24 (−0.50, 0.02)	0.07	0	0
WBC (/μL)	1	−253.00 (−781.10, 275.10)	0.35	−253.00 (−781.10, 275.10)	0.35	0	0
AKP (U/L)	2	28.27 (12.61, 43.93)	0.0004	28.27 (12.61, 43.93)	0.0004	0.91	0
Osteoprotegerin (pg/mL)	1	13.00 (−34.38, 60.38)	0.59	13.00 (−34.38, 60.38)	0.0004	0	0
sRANKL (pg/mL)	1	−2.90 (−8.62, 2.82)	0.32	−2.90 (−8.62, 2.82)	0.32	0	0
Deoxypyridoline (nmol/L)	1	46.00 (4.55, 87.45)	0.03	46.00 (4.55, 87.45)	0.03	0	0
Triglycerides (mg/dL)	4	−11.33 (−30.11, 7.44)	0.24	−11.33 (−30.11, 7.44)	0.24	0.96	0
CRP (mg/dL)	5	−0.01 (−0.29, 0.26)	0.93	−0.13 (−0.19, −0.06)	0.0002	0.02	65
Uric acid (mg/dL)	1	0.03 (−0.50, 0.56)	0.91	0.03 (−0.50, 0.56)	0.91	0	0
HbA1c (%)	1	−0.64 (−1.08, −0.20)	0.004	−0.64 (−1.08, −0.20)	0.004	0	0
BSAP (U/L)	2	8.79 (4.29, 13.29)	0.0001	8.79 (4.29, 13.29)	0.0001	0.76	0

Notes: WMD: weighted mean difference; iPHT: intact parathyroid hormone; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; WBC: white blood counts; AKP: alkaline phosphatase; sRANKL: soluble receptor activator of nuclear factor-κB ligand; CRP: C-reactive protein; HbA1c: glycated hemoglobin; BSAP: bone-specific alkaline phosphatase.

Figure 4. Forest plots of main effects of NCBP and CBP on serum iPTH levels. NCBP = non-calcium-based phosphate binders; CBP = calcium-based phosphate binders; iPTH = intact parathyroid hormone; WMD = weighted mean differences.

Figure 5. Forest plots of main effects of NCBP and CBP on serum calcium levels. NCBP = non-calcium-based phosphate binders; CBP = calcium-based phosphate binders; WMD = weighted mean differences.

Figure 6. Forest plots of main effects of NCBP and CBP on bone histomorphometry. NCBP = non-calcium-based phosphate binders; CBP = calcium-based phosphate binders; WMD = weighted mean differences.

Figure 7. Funnel plot based on WMD for serum calcium levels. WMD = weighted mean differences.

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