scholarly journals Short-Term Effects of Very-Low-Phosphate and Low-Phosphate Diets on Fibroblast Growth Factor 23 in Hemodialysis Patients

2019 ◽  
Vol 14 (10) ◽  
pp. 1475-1483 ◽  
Author(s):  
Wan-Chuan Tsai ◽  
Hon-Yen Wu ◽  
Yu-Sen Peng ◽  
Shih-Ping Hsu ◽  
Yen-Ling Chiu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Mean Difference ◽  
Fibroblast Growth ◽  
Short Term ◽  
Protein Ratio ◽  
Fgf23 Level ◽  
Lowering Effect

Background and objectivesThe short-term effects of low-phosphate diets on fibroblast growth factor 23 (FGF23) level and the optimal amount of dietary phosphate restriction in patients undergoing hemodialysis remain unknown.Design setting, participants, & measurementsThis was a randomized, active-controlled trial with a crossover design that included 35 adults with ESKD undergoing thrice-weekly hemodialysis and with a serum phosphate level >5.5 mg/dl or between 3.5 and 5.5 mg/dl with regular phosphate binder use at a hemodialysis unit of tertiary teaching hospital in Taiwan. Subjects were randomized 1:1 to receive a very-low-phosphate diet, with a phosphate-to-protein ratio of 8 mg/g, or a low-phosphate diet, with a phosphate-to-protein ratio of 10 mg/g for 2 days, each with a 5-day washout during which subjects adhered to their usual diet. The primary outcome measure was mean difference in change-from-baseline intact FGF23 level between intervention groups. Secondary outcomes included difference in change-from-baseline serum phosphate, intact parathyroid hormone (PTH), and C-terminal FGF23 level between intervention groups.ResultsThere was no significant difference in the mean change-from-baseline in intact FGF23 levels between the two study diets. The very-low-phosphate diet significantly lowered serum phosphate (mean difference, 0.6 mg/dl; 95% confidence interval [95% CI], 0.2 to 1.0; P=0.002). There were no significant differences in change-from-baseline intact PTH and C-terminal FGF23 levels between the two study diets.ConclusionsOver the 2-day period, the FGF23-lowering effect of the very-low-phosphate diet is similar to that of the low-phosphate diet. The very-low-phosphate diet has an additional phosphate-lowering effect compared with the low-phosphate diet.

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 Short-term effects of sevelamer-carbonate on fibroblast growth factor 23 and pulse wave velocity in patients with normophosphataemic chronic kidney disease Stage 3

2019 ◽  
Vol 12 (5) ◽  
pp. 678-685 ◽  
Author(s):  
Annet Bouma-de Krijger ◽  
Frans J van Ittersum ◽  
Tiny Hoekstra ◽  
Pieter M ter Wee ◽  
Marc G Vervloet
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Pulse Wave Velocity ◽  
Fibroblast Growth Factor ◽  
Pulse Wave ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Short Term ◽  
Sevelamer Carbonate

Abstract Background High concentrations of both phosphate and fibroblast growth factor 23 (FGF23) observed in chronic kidney disease (CKD) are associated with an increased risk of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) is a surrogate marker for cardiovascular events and all-cause mortality. It is not known whether a reduction of FGF23 or phosphate alters cardiovascular risk. Sevelamer has shown to have the ability to reduce both phosphate and FGF23 concentrations. Furthermore, reduction of PWV is reported with sevelamer use as well, but it is unclear if this is mediated by decline of phosphate or FGF23. We investigated if sevelamer induced a decline in PWV and if this was associated with a reduction in FGF23. Methods In all, 24 normophosphataemic CKD Stage 3 patients started treatment with a fixed dose of sevelamer-carbonate (Renvela®) 2.4 g twice daily, with their usual diet for 8 weeks in a single-arm study. PWV was measured and blood samples were obtained before, during and after washout of treatment with sevelamer. Vascular calcification was quantified using the Kauppila Index (KI). The primary outcome was the change of PWV from baseline to 8 weeks of treatment and the secondary endpoint was the difference of FGF23 following treatment with sevelamer. One of the linear mixed models was used to analyse the association between treatment and outcome. Mediation analysis was performed as a sensitivity analysis. The study was registered in the Dutch trial register (http://www.trialregister.nl: NTR2383). Results A total of 18 patients completed 8 weeks of treatment with sevelamer and were analysed. Overall, treatment with sevelamer did not induce a significant reduction of PWV (β = −0.36, P = 0.12). However, in patients with less vascular calcification (lower KI score), there was a statistically significant reduction of PWV, adjusted for mean arterial pressure, after treatment (β = 0.63, P = 0.02). Addition of FGF23 to the model did not alter this association. Mediation analysis yielded similar results. FGF23 did not decrease during treatment with sevelamer. Conclusion In this short-term pilot study in normophosphataemic CKD patients, treatment with sevelamer did not improve PWV. In subgroup analysis, however, PWV improved in patients with no or limited abdominal aorta calcifications. This was not associated with a decline of FGF23.

scholarly journals Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

2015 ◽  
Vol 6 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Shahanas Chathoth ◽  
Samir Al-Mueilo ◽  
Cyril Cyrus ◽  
Chittibabu Vatte ◽  
Awatif Al-Nafaie ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Control Group ◽  
Phosphorus Metabolism ◽  
Fibroblast Growth ◽  
Saudi Population ◽  
Fgf23 Level

Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

scholarly journals Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer

2018 ◽  
Vol 25 (3) ◽  
pp. 153 ◽  
Author(s):  
Amir Ghorbanihaghjo ◽  
Hassan Argani ◽  
Zahra Golmohamadi ◽  
Nadereh Rashtchizadeh ◽  
Mehran Mesgari Abbasi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Fibroblast Growth

scholarly journals SUN-059 Significance of fibroblast growth factor-23 (FGF23) level in hemodialysis patients

2019 ◽  
Vol 4 (7) ◽  
pp. S179
Author(s):  
M. Tashiro ◽  
H. Shima ◽  
T. Inoue ◽  
K. Kawahara ◽  
K. Miya ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Hemodialysis Patients ◽  
Fibroblast Growth ◽  
Fgf23 Level

scholarly journals Fibroblast Growth Factor-23 (FGF23) in Patients with Transient Hypoparathyroidism: Its Important Role in Serum Phosphate Regulation

2007 ◽  
Vol 54 (3) ◽  
pp. 465-470 ◽  
Author(s):  
Hiroyuki YAMASHITA ◽  
Yuji YAMAZAKI ◽  
Hisashi HASEGAWA ◽  
Takeyoshi YAMASHITA ◽  
Seiji FUKUMOTO ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Fibroblast Growth ◽  
Phosphate Regulation ◽  
Transient Hypoparathyroidism

scholarly journals Relationship between Fibroblast Growth Factor-23 and Mineral Metabolism in Chronic Kidney Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Kosaku Nitta
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Serum Phosphate ◽  
Maintenance Hemodialysis ◽  
Fibroblast Growth ◽  
Fgf 23

Fibroblast growth factor- (FGF-)23 is a recently discovered regulator of calcium-phosphate metabolism. FGF-23 appears to decrease in synthesis and accelerated degradation of 1,25(OH)2D. Together with its cofactor Klotho, FGF-23 maintains serum phosphate levels within the normal range by increasing renal phosphate excretion. In chronic kidney disease (CKD), FGF-23 levels rise in parallel with the decline in renal function long before a significant increase in serum phosphate concentration occurs. Both Klotho and FGF-23, linked by a receptor mechanism, affect vitamin D synthesis and parathyroid hormone (PTH) secretion. Previous studies have shown a close association between reduced FGF-23 or Klotho activities and vascular calcification. The possible association of FGF-23 and left ventricular hypertrophy or vascular dysfunction has been proposed. Finally, prospective studies have shown that high serum FGF-23 concentrations predict more rapid disease progression in CKD patients who were not on dialysis and increased mortality in patients on maintenance hemodialysis. FGF-23 may therefore prove to be an important therapeutic target for the management of CKD.

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.

scholarly journals Fibroblast Growth Factor 23 Is Increased in Calcium Nephrolithiasis with Hypophosphatemia and Renal Phosphate Leak

2006 ◽  
Vol 91 (3) ◽  
pp. 959-963 ◽  
Author(s):  
Domenico Rendina ◽  
Giuseppe Mossetti ◽  
Gianpaolo De Filippo ◽  
Michele Cioffi ◽  
Pasquale Strazzullo
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Phosphate Concentration ◽  
Hypophosphatemic Rickets ◽  
Fibroblast Growth ◽  
Oncogenic Osteomalacia ◽  
Stone Formers ◽  
Fgf23 Concentration

Abstract Context: Nephrolithiasis affects about 10% of the population in industrialized countries, with calcium salts composing more than 80% of renal stones. A significant percentage of patients with calcium nephrolithiasis and normal parathyroid function show hypophosphatemia and reduced renal phosphate reabsorption (i.e. a renal phosphate leak). Objectives: The objective of the study was to compare serum levels of fibroblast growth factor 23 (FGF23), a regulator of phosphate homeostasis, in 110 recurrent stone formers with or without renal phosphate leak, six patients affected by X-linked hypophosphatemic rickets, five patients affected by oncogenic osteomalacia, and 60 unrelated healthy controls. Design: This was a prospective interventional study. Methods: Renal phosphate leak was identified based on the occurrence of idiopathic hypophosphatemia [serum phosphate concentration < 2.50 mg/dl (<0.80 mmol/liter)] and reduced renal threshold phosphate concentration [<2.2 mg/liter (<0.70 mmol/liter)]. Results: In 22 stone formers with renal phosphate leak, serum FGF23 concentration was significantly higher as compared with 88 stone formers without renal phosphate leak and with controls [83.3 (65.6–101.1) vs. 32.1 (26.8–37.4) and 24.5 (19.8–29.1) reference units (RU)/ml, respectively]. Stone formers with renal phosphate leak showed lower FGF23, compared with patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets [572.3 (235.9–908.7) RU/ml]. Among stone formers and controls, serum FGF23 concentration displayed a strong inverse association with serum phosphate (r = −0.784, P = 0.009) and the rate of tubular phosphate reabsorption (r = −0.791, P = 0.008). Conclusions: In our study population, renal phosphate leak affected 20% of stone formers and was strongly associated with increased serum FGF23 concentration.

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