Abstract: TH-OR038
Ferric Citrate Reduced FGF23 in Patients with Non-Dialysis Dependent Chronic Kidney Disease (NDD-CKD) and Iron Deficiency Anemia (IDA) Irrespective of the Change in Serum Phosphate (P)
Session Information
- Clinical Trials in CKD Tubulointerstitium
November 02, 2017 | Location: Room 392, Morial Convention Center
Abstract Time: 05:54 PM - 06:06 PM
Category: Chronic Kidney Disease (Non-Dialysis)
- 305 CKD: Clinical Trials and Tubulointerstitial Disorders
Authors
- Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States
- Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
- Uhlig, Katrin, Keryx Biopharmaceuticals, Boston, Massachusetts, United States
- Neylan, John F., Keryx Biopharmaceuticals, Boston, Massachusetts, United States
- Fishbane, Steven, Hofstra Northwell Health, Commack, New York, United States
- Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
Background
Ferric citrate (FC), an oral iron-based P binder approved for control of serum P in patients (pts) with CKD on dialysis, has also been shown to improve hemoglobin (Hb) and iron parameters in pts with NDD-CKD with IDA. FGF23 is a key phosphate-regulating hormone and known to be elevated in patients with iron deficiency. Here, in a post hoc analysis of a phase 3 study, we examine effects of FC on FGF23 in pts stratified by baseline (BL) P and transferrin saturation (TSAT).
Methods
233 pts with NDD-CKD and IDA were randomized 1:1 to receive FC (n=117) or placebo (n=116) for 16 wks. FC was initiated at 3 1-g tablets/day and titrated to achieve an increase in Hb ≥1 g/dL from BL (max 12 g/day). The effect of FC on both intact (i) and c-terminal (c)-FGF23 are reported by BL strata of P and TSAT, and the effect of FC on serum P are shown stratified by BL P.
Results
BL levels of iFGF23 and cFGF23 were positively related to BL P. After 16 wks of FC treatment, iFGF23 concentrations significantly decreased in both TSAT strata and across all strata of BL P except in pts with BL P <3.5 mg/dL. cFGF23 significantly decreased in both TSAT strata, and in all BL P strata except the highest (≥5.5 mg/dL). Changes in FGF23 did not consistently track with P changes [Table].
Conclusion
In pts with NDD-CKD and IDA, 16 wks of treatment with FC significantly reduced iFGF23 except in pts with the lowest BL P, while cFGF23 was significantly reduced except in pts with the highest BL P. iFGF23 and cFGF23 reductions occurred irrespective of BL TSAT, BL P and P change. These data suggest that FC reduces FGF23 via several, potentially independent pathways in pts with CKD and IDA.
| BL P <3.5 mg/dL | BL P 3.5 - <4.5 mg/dL | BL P 4.5 - <5.5 mg/dL | BL P ≥5.5 mg/dL | BL TSAT <20% | BL TSAT ≥20% | ||
| i-FGF23 (pg/mL) [n=117] | BL median (IQR) [n] | 89.7 (66.6, 109.4) [16] | 118.1 (86.3, 176.7) [65] | 205.3 (127.4, 347.9) [25] | 250.2 (177.4, 1612.5) [11] | 117.1 (84.3, 246.4) [58] | 143.5 (95.1, 227.6) [59] |
| 16 wks median (IQR) [n] | 85.0 (57.1, 92.5) [13] | 102.2 (66.7, 154.9) [46] | 152.0 (93.2, 309.1) [20] | 156.6 (101.4, 255.2) [ 7] | 101.4 (59.7, 156.6) [41] | 113.0 (75.3, 192.2) [45] | |
| p-value* | 0.340 | 0.004 | 0.012 | 0.031 | <0.001 | 0.019 | |
| c-FGF23 (RU/mL) [n=116] | BL median (IQR) [n] | 266.0 (155.3, 406.7) [16] | 330.5 (153.4, 546.9) [64] | 415.8 (231.7, 931.7 [25] | 576.8 (474.1, 1554.1) [11] | 427.4 (215.4, 934.5) [57] | 297.8 (164.9, 474.1) [59] |
| 16 wks median (IQR) [n] | 173.1 (136.1, 256.9) [13] | 198.3 (117.3, 293.5) [45] | 328.0 (210.8, 588.7 [20] | 592.1 (332.2, 898.5) [ 7] | 259.3 (156.3, 409.2) [40] | 207.1 (121.3, 385.8) [45 | |
| p-value* | 0.021 | <0.001 | 0.027 | 0.297 | <0.001 | 0.009 | |
| Serum P (mg/dL) [n=115] | Δ (BL to wk 16) mean±SE | +0.24±0.14 | -0.26±0.08 | -0.97±0.15 | -1.74±0.63 | - | - |
| p-value† | 0.115 | 0.002 | <0.001 | 0.032 | - | - | |
* p-values are from a non-parametric (Wilcoxon signed-rank) test; †p-values are from a parameter t-test; IQR = Interquartile Range
Funding
- Commercial Support –