Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

2018 ◽  
Vol 47 (6) ◽  
pp. 406-414 ◽  
Author(s):  
Noriaki Maruyama ◽  
Tomoyasu Otsuki ◽  
Yoshinori Yoshida ◽  
Chinami Nagura ◽  
Maki Kitai ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Hemodialysis Patients ◽  
Serum Phosphate ◽  
Lanthanum Carbonate ◽  
Ferric Citrate ◽  
Control Group ◽  
Serum Phosphate Level ◽  
Fibroblast Growth

Background: Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. Methods: This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. Results: FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline –6,160 vs. –1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). Conclusion: In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level.

scholarly journals SP387COMPARISON OF THE SUPPRESSIVE EFFECTS ON FIBROBLAST GROWTH FACTOR 23 BETWEEN FERRIC CITRATE AND LANTHANUM CARBONATE

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii244-iii244 ◽  
Author(s):  
Akira Fujimori ◽  
Satoshi Ohkawa ◽  
Shioko Okada ◽  
Noriko Mizobuchi ◽  
Makoto Sakai ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Lanthanum Carbonate ◽  
Ferric Citrate ◽  
Fibroblast Growth

scholarly journals Favorable Effects of Burosumab on Fibroblast Growth Factor 23-Related Osteomalacia: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A194-A194
Author(s):  
Yuki Oe ◽  
Hiraku Kameda ◽  
Hiroshi Nomoto ◽  
Keita Sakamoto ◽  
Takeshi Soyama ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Serum Phosphate Level ◽  
Fibroblast Growth ◽  
Venous Sampling ◽  
Dihydroxyvitamin D ◽  
Fgf23 Level ◽  
1,25 Dihydroxyvitamin D

Abstract Background: Fibroblast growth factor 23 (FGF23) decreases serum phosphate levels by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption by decreasing serum 1,25-dihydroxyvitamin D level, thereby regulating phosphate metabolism. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by FGF23 overproduction by tumor tissue. Resecting the responsible tumor is a radical treatment for TIO. When the responsible tumor is undetectable, phosphate and active vitamin D administration is recommended. However, supplementation alone is frequently insufficient to maintain phosphate levels and it is difficult to prevent the complications associated with medical therapy, including hypercalciuria and nephrocalcinosis. Recently, burosumab, a human monoclonal anti-FGF23 antibody, has been approved in Japan as a therapeutic agent for FGF23-related hypophosphatemia. Here, we present a patient with TIO effectively treated with burosumab in the absence of identification of tumour location. Clinical case: A 47-year-old female developed pain and edema of the feet; however, the cause could not be determined at local hospitals. Afterwards, she developed marked bone atrophy in the feet and was referred to our hospital. Her age at symptom onset, hypophosphatemia (serum P, 1.9 mg/dl, 2.7 mg/dl < n < 4.6 mg/dl), high serum FGF23 level (630 pg/ml, 16 pg/ml < n < 69 pg/ml), and decreased 1,25-dihydroxyvitamin D level (12.9 pg/ml, 20 pg/ml < n < 60 pg/ml) indicated FGF23-related osteomalacia. She was not having any medication at the time of diagnosis, including saccharified iron oxide or iron polymaltose. Urinary phosphate excretion increased without renal tubular defect; therefore, hypophosphatemic osteomalacia was diagnosed. MRI showed high signal intensity in the talus, sacral, and L5 vertebral regions, indicating multiple pseudofractures. Comprehensive imaging studies, including systemic CT scan and 111In-pentetreotide scintigraphy, did not reveal any tumors despite the suspicion of TIO. Next, we performed systemic venous sampling, which revealed high FGF23 level in the left external iliac vein. Second venous sampling limited to the left lower limb exhibited high FGF23 level in the posterior tibial vein. However, an additional imaging study limited to the left foot could not identify any tumors. Genetic variation was negative for potentially responsible genes, including PHEX and FGF23. We decided to administer burosumab to normalize serum phosphate level without phosphate supplementation. Within 2 months, pain was relieved and the visual analog scale scores also improved from 10 to 6. Moreover, bone MRI showed improved pseudofractures. Conclusion: Burosumab administration was effective for TIO of unknown origin, and it improved not only laboratory findings but also clinical symptoms in this case.

scholarly journals Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial

2019 ◽  
Vol 30 (6) ◽  
pp. 1096-1108 ◽  
Author(s):  
Joachim H. Ix ◽  
Tamara Isakova ◽  
Brett Larive ◽  
Kalani L. Raphael ◽  
Dominic S. Raj ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Gastrointestinal Symptoms ◽  
Phosphate Transport ◽  
Serum Phosphate ◽  
Lanthanum Carbonate ◽  
Phosphate Binders ◽  
Fibroblast Growth ◽  
Baseline Serum

BackgroundHigher serum phosphate and fibroblast growth factor-23 (FGF23) levels may be modifiable to prevent cardiovascular disease in CKD. Short-term studies have reported modest efficacy in phosphate and FGF23 reduction with intestinal phosphate binders in CKD.MethodsTo investigate effects of lanthanum carbonate (LC; a phosphate binder) and/or nicotinamide (NAM; an inhibitor of active intestinal phosphate transport) on serum phosphate and FGF23 in stage 3b/4 CKD, we conducted a randomized trial among individuals with eGFR 20–45 ml/min per 1.73 m2 to NAM (750 mg twice daily) plus LC (1000 mg thrice daily), NAM plus LC placebo, LC plus NAM placebo, or double placebo for 12 months. Dual primary end points were change from baseline in serum phosphate and intact FGF23 concentrations.ResultsMean eGFR for the 205 participants was 32ml/min per 1.73 m2. At baseline, serum phosphate was 3.7 mg/dl and median FGF23 was 99 pg/ml (10th, 90th percentiles: 59, 205). Mean rates of change in phosphate increased slightly over 12 months in all groups and did not differ significantly across arms. Similarly, percent changes in FGF23 per 12 months increased for all arms except LC plus placebo, and did not differ significantly across arms. Gastrointestinal symptoms limited adherence. Adverse events rates were similar across arms.ConclusionsLC and/or NAM treatment did not significantly lower serum phosphate or FGF23 in stage 3b/4 CKD over 12 months. Although these agents appeared safe, intestinal symptoms limited adherence. Reducing phosphate and FGF23 in nondialysis CKD will require new approaches.

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