Table 4.
Responsiveness of FGF23 concentration to oral phosphate binder use in randomized controlled trials of CKD and dialysis cohorts
| Study | Duration | Sample Size (n); CKD | Diet/Phosphate Intake | Binder/Dose | FGF23 Assay | FGF23 and Mineral Response |
|---|---|---|---|---|---|---|
| Binder versus placebo | ||||||
| Block et al. (99) | 9 mo | 148; CKD stages 3 and 4; serum P=3.5–6.0 mg/dl | Not controlled | Composite active group: LaCO3, CaAc, SCO3; mean=2700, 5900, 6300 mg/d, respectively | cFGF23/iFGF23 | cFGF23/iFGF23: no change in active versus placebo; cFGF23: no difference between binder types; iFGF23: decrease in patients on SCO3, increase in patients on CaAc; modest decrease in serum P (4.2–3.9 mg/dl) and FEP (32%–26%) in active arm |
| Isakova et al. (91) | 3 mo (2×2) | 39; CKD stages 3 and 4 normophosphatemic | Ad libitum versus 900 mg | LaCO3: fixed 3000 mg/d | cFGF23 | Neither LaCO3 nor 900 mg P diet alone reduced levels compared with placebo or ad libitum diet; variable reduction 35% (±32%) with dual LaCO3 and 900 mg P but baseline cFGF23 much higher in this group (mean=514 versus 99, 127, 120 RU/ml); no change in serum P or FEP |
| Chue et al. (107) | 9 mo | 109; CKD stage 3 normophosphatemic | Not controlled | LaCO3: fixed 1600 mg/d | iFGF23 | No change on active therapy (median decrease=5 pg/ml); no change in serum P or FEP |
| Seifert et al. (144) | 12 mo | 38; CKD stage 3 normophosphatemic | Not controlled | LaCO3: fixed 3000 mg/d | iFGF23 | No change in LaCO3 versus placebo; no change in serum or 24-h urine P |
| Calcium-based binder versus noncalcium-based binder | ||||||
| CKD | ||||||
| Oliveira et al. (145) | 1.5 mo | 40; CKD stages 3 and 4 normophosphatemic | Dietary monitoring; 739±253 mg/d | CaAc versus SHCl; titrated, doubled every 2 wk | iFGF23 | No change with CaAc (although trend to reduction); reduction by week 6 with SHCl (median decrease=49 pg/ml, 48%).; no change in serum P but decrease in FEP in both groups |
| Yilmaz et al. (105) | 2 mo | 100; CKD stage 4 hyperphosphatemic | Not controlled | CaAc versus SHCl; titrated to serum P<5.5 mg/dl | iFGF23 | No change with CaAc (mean increase=4%); mean 27% reduction with SHCl (−33% to −9%); greater reduction in serum P with SHCl (mean decrease=31% versus 15%) |
| Vlassara et al. (106) | 2 wk (crossover) | 22; CKD stages 2–4; diabetic | Dietary monitoring; 967±479 mg/d | CaCO3 versus SCO3; fixed 3600 versus 4800 mg/d | iFGF23 | Nonsignificant trend to reduction with SCO3 and increase with CaCO3; significant decrease with SCO3 treatment in patients with baseline concentration>70 pg/ml; no change in serum P but decrease in 24-h urine P |
| Soriano et al. (146) | 4 mo | 32; CKD stages 4 and 5 hyperphosphatemic | Standardized diet: 1 g/kg per day protein; <800 mg P | CaCO3 versus LaCO3; titrated to serum P (<4.5 mg/dl) | iFGF23 | No reduction with CaCO3 but significant decrease with LaCO3 (mean decrease=36%); no change in serum P but decrease in FEP in LaCO3 arm |
| Hemodialysis | ||||||
| Koiwa et al. (147) | 1 mo | 46; prevalent HD | Not controlled | CaCO3 versus SHCl+CaCO3; fixed 3000 mg/d CaCO3 versus 3000 mg/d SHCl+3000 mg/d CaCO3 | iFGF23 | Reduction with CaCO3+SHCl but not with CaCO3 alone; levels increased in 8 of 26 patients on SHCl+CaCO3 therapy |
| Cancela et al. (148) | 12 mo | 71; prevalent HD | Not controlled | CaAc versus SHCl; titrated to achieve serum P, iCal, iPTH targets | iFGF23 | Substantial reduction in patients receiving SHCl over 1 yr (median decrease=17,508–4627 pg/ml) but no change in patients on CaAc |
| Toida et al. (149) | 3 mo (crossover) | 42; prevalent HD | Not controlled | CaCO3 versus LaCO3; titrated to achieve serum P, iCal, iPTH targets | iFGF23 | No change with CaCO3 but reduction with LaCO3 (mean decrease=46%) |
P, phosphate; LaCO3, lanthanum carbonate; CaAc, calcium acetate; SCO3, sevelamer carbonate; SHCl, sevelamer hydrochloride; CaCO3, calcium carbonate; HD, hemodialysis; iCal, ionized calcium; iPTH, intact PTH.