Table 2.

Overview of studies with phosphate binders with or without dietary phosphate restriction to lower FGF23

	Total no.	Study design	Duration of intervention	Age, years	Baseline characteristics			FGF23 assay	Intervention		Change in FGF23
					eGFR (ml/min)	Pi (mg/dl)	FGF23		Diet	Medication
CKD
Oliveira et al. [124]	40	Randomized trial, up titration med. every 2 weeks	6 weeks	50	35	3.5	97 pg/ml	Intact (Kainos)	Fixed 615 mg protein/day	Calcium acetate 1.32 g/day– > 2.64 g/day– > 5.3 g/day	No change
										Sevelamer HCT 1.6 g/day– > 3.2 g/day– > 6.4 g/day	Reduction
Isakova et al. [121]	16	2 × 2 factorial placebo controlled trial	2 weeks	62	40	3.2	158	c-term (Immutopics)	Pi diet 750 mg/day	Placebo	No change
									Pi diet 1500 mg/day	Lanthanum carbonate 3 g/day	No change
									Pi diet 750 mg/day	Lanthanum carbonate 3 g/day	No change
									Pi diet 1500 mg/day	Placebo	Increase
Gonzalez-Parra et al. [130]	18	Open label trial	4 weeks	70	42	3.5	212 RU/ml	c-term (Immutopics)	Fixed protein 0.8 mg/kg/day	Lanthanum carbonate 2250 mg/day	Reduction (22%)
Yilmaz et al. [125]	100	Randomized open label trial	8 weeks	45	24	7.7	40 pg/ml	Intact (Kainos)	NA	Sevelamer 1.6 g/day, up titrated to Pi < 5.5 mg/dl	Reduction (27%)
										Calcium acetate 3 g/day, up titrated to Pi < 5.5 mg/dl	No change
Bleskestad et al. [137]	21	Open label cross-over trial	2 × 2 weeks, 2 weeks wash-out in between	66	37	3.3	90/110 pg/ml	Intact (Kainos)	Ad Libitum diet	Alfacalcidol 0.25 μg/day– > Sevelamer 1.6 g/day	No change
										Sevelamer 1.6 g/day– > Alfacalcidol 0.25 μg/day	Increase (NS)
Vlassara et al. [126]	20	Open label cross-over trial	2 × 8 weeks, 1 week wash-out in between	61	38	4.0	95 μg/ml	NA (Genzyme diagnostics)	Ad Libitum diet, mean Pi intake 967 g/day	Sevelamer 4.8 g/day– > calcium carbonate 3.6 g/day	No change
										Calcium carbonate 3.6 g/day– > Sevelamer 4.8 g/day	Reduction in group with FGF23 baseline > 70 μg/ml
Block et al. [127]	148	Double blind RCT	9 months	68	32	4.2	120 pg/ml 227 RU/ml	Intact (Kainos) and c-term (Immutopics)	Ad Libitum diet	Calcium acetate av. 5.9 g/day	Increase
										Lanthanum carbonate av. 2.7 g/day	No change
										Sevelamer av. 6.3 g/day	Reduction of iFGF23, No change of cFGF23
										Placebo	No change
Isakova et al. [122]	39	2 × 2 factorial single blinded placebo controlled trial	12 weeks	55	38	3.6	129 RU/ml	c-term (Immutopics)	Ad Libitum diet	Placebo	No change
									Pi diet 900 mg/day	Lanthanum carbonate 3 g/day	No change
									Ad Libitum diet	Placebo	No change
									Pi diet 900 mg/day	Lanthanum carbonate 3 g/day	Reduction
Seifert et al. [135]	38	Double blind RCT	12 months	62/61	47/45	3.5/3.3	69/55 pg/ml	Intact (Kainos)	Ad Libitum	Placebo	No change
										Lanthanum carbonate 3 g/day	No change
Chue et al. [133]	109	Double blind RCT	36 weeks	55	50	3.2	69 pg/ml	Intact (Kainos)	Ad Libitum	Placebo	No change
										Sevelamer 1.6 g/each meal	No change, reduction only when adherence to medication was ≥ 80%
Spatz et al. [138]	40	Prospective open cohort study	12 weeks	70	21	4.8	602 RU/ml	c-term (Immutopics)	Verbal instruction for low Pi diet	Sevelamer 2.4 g/day up titrated on serum Pi	No change
Liabeuf et al. [134]	78	Double blind RCT	12 weeks	63	27	3.8	157 RU/ml, 72 pg/ml	c-term and intact (both Immutopics)	Ad Libitum	Sevelamer fixed dose 4.8 g/day	No change (both iFGF23 and cFGF23)
										Placebo	No change
Bouma-de Krijger et al. [140]	24	Prospective open cohort study	8 weeks	52	44	3.5	167 RU/ml	c-term (Immutopics)	Ad Libitum	Sevelamer fixed dose 4.8 g/day	No change
Ix et al. [136]	205	Double blind RCT (COMBINE trial)	12 months	69	32	3.7	99 pg/ml	Intact (Kainos)	Verbal instruction for low Pi diet	Nicotamide 225 mg/day +placebo	No change
										Nicotamide 225 mg/day + lanthanum carbonate 3 g/day	No change
										Placebo + lanthanum carbonate 3 g/day	No change
										Placebo + placebo	No change
Dialysis
Koiwa et al. [128]	46	Open label randomized trial	4 weeks	57	Dialysis	5.9	9000 ng/l	Intact (manufacturer NA)	NA	Sevelamer 3 g/day + calcium carbonate 3 g/day	Reduction
										Calcium carbonate 3 g/day	No change
Brandenburg et al. [139]	75	Open label cohort study	8 weeks	65	Dialysis	6.4	7244 RU/ml	c-term (Immutopics)	NA	Sevelamer titration on top of usual Pi-binder medication to serum Pi < 5.5 mg/dl	No change
Chang et al. [129]	25	Open label randomized trial	8 weeks	56/61	Dialysis	6.8/6.5	8678/8565 pg/ml	Intact (Kainos)	Pi diet 600-800 mg/day	Lanthanum carbonate up titrated to serum Pi	Reduction
										Calcium carbonate up titrated to serum Pi	No change
Zhang et al. [131]	92	Open label randomized trial	12 months	48	Dialysis	8.0/7.7	348/328 pg/ml	Intact (Biochamp China)	NA	Lanthanum carbonate up titrated to serum Pi < 5.5 mg/dl	Reduction
										Calcium carbonate up titrated to serum Pi < 5.5 mg/dl	No change
Ketteler et al. [132]	1059	Multi centre open label phase 3 study	24 weeks and a subset of no. 549 up to 1 year	56	Dialysis	7.4	39600 pg/ml	Intact (Immutopics)	NA	Sucroferric hydroxide 1–3 g/day	Reduction at 24 and at 52 weeks
										Sevelamer 2.4–14.4 g/day	Reduction at 24 and at 52 weeks
											Pooled analysis 64% reduction at 52 weeks

Overview of studies with phosphate binders with or without dietary phosphate restriction to lower FGF23

FGF23 fibroblast growth factor 23, factor-23, eGFR estimated glomerular filtration rate, iFGF23 intact FGF23, c-term carboxy terminal fragment of FGF23, Pi serum phosphate, NA not available