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Model-Based Analysis of FGF23 Regulation in Chronic Kidney Disease.

Yokota H, Pires A, Raposo JF, Ferreira HG - Gene Regul Syst Bio (2010)

Bottom Line: The model also predicted that the administration reduced a urinary output of phosphorous.This model-based prediction indicated that the therapeutic reduction of FGF23 by the neutralizing antibody did not reduce phosphorus burden of CKD patients and decreased the urinary phosphorous excretion.The results herein indicate that it is necessary to understand the mechanism in CKD in which the level of FGF23 is elevated without effectively regulating phosphorus.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.

ABSTRACT
The mechanism of FGF23 action in calcium/phosphorus metabolism of patients with chronic kidney disease (CKD) was studied using a mathematical model and clinical data in a public domain. We have previously built a physiological model that describes interactions of PTH, calcitriol, and FGF23 in mineral metabolism encompassing organs such as bone, intestine, kidney, and parathyroid glands. Since an elevated FGF23 level in serum is a characteristic symptom of CKD patients, we evaluate herein potential metabolic alterations in response to administration of a neutralizing antibody against FGF23. Using the parameters identified from available clinical data, we observed that a transient decrease in the FGF23 level elevated the serum concentrations of PTH, calcitriol, and phosphorus. The model also predicted that the administration reduced a urinary output of phosphorous. This model-based prediction indicated that the therapeutic reduction of FGF23 by the neutralizing antibody did not reduce phosphorus burden of CKD patients and decreased the urinary phosphorous excretion. Thus, the high FGF23 level in CKD patients was predicted to be a failure of FGF23-mediated phosphorous excretion. The results herein indicate that it is necessary to understand the mechanism in CKD in which the level of FGF23 is elevated without effectively regulating phosphorus.

No MeSH data available.


Related in: MedlinePlus

Linkage of the FGF23 concentration in serum ([FGF23]AB) and the P concentration ([P]) in serum. A) [P] in healthy populations. B) [P] in patients with tumor induced osteomalacia. (C) and (D) [P] and the renal threshold for P in patients with Fibrous Dysplasia. E) [P] in patients with XLH.
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f3-grsb-2010-053: Linkage of the FGF23 concentration in serum ([FGF23]AB) and the P concentration ([P]) in serum. A) [P] in healthy populations. B) [P] in patients with tumor induced osteomalacia. (C) and (D) [P] and the renal threshold for P in patients with Fibrous Dysplasia. E) [P] in patients with XLH.

Mentions: Since a primary known role of FGF23 is regulation of the serum level of P, we evaluated the dependence of P on the modified FGF23 level in healthy populations, and patients with Tumor Induced Osteomalacia, Fibrous Dysplasia, and XLH (Fig. 3). In all groups, a positive correction was observed between the level of P and the modified level of FGF23 in serum. Note that CKD data in Figure 2D showed the elevated P level up to 6 mg/dl, while the higher bound of the P level was ∼2 mg/dl (Tumor Induced Osteomalacia), 3.5 ∼4 mg/dl (Fibrous Dysplasia and XLH), and 4.5 mg/dl (healthy populations).


Model-Based Analysis of FGF23 Regulation in Chronic Kidney Disease.

Yokota H, Pires A, Raposo JF, Ferreira HG - Gene Regul Syst Bio (2010)

Linkage of the FGF23 concentration in serum ([FGF23]AB) and the P concentration ([P]) in serum. A) [P] in healthy populations. B) [P] in patients with tumor induced osteomalacia. (C) and (D) [P] and the renal threshold for P in patients with Fibrous Dysplasia. E) [P] in patients with XLH.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901635&req=5

f3-grsb-2010-053: Linkage of the FGF23 concentration in serum ([FGF23]AB) and the P concentration ([P]) in serum. A) [P] in healthy populations. B) [P] in patients with tumor induced osteomalacia. (C) and (D) [P] and the renal threshold for P in patients with Fibrous Dysplasia. E) [P] in patients with XLH.
Mentions: Since a primary known role of FGF23 is regulation of the serum level of P, we evaluated the dependence of P on the modified FGF23 level in healthy populations, and patients with Tumor Induced Osteomalacia, Fibrous Dysplasia, and XLH (Fig. 3). In all groups, a positive correction was observed between the level of P and the modified level of FGF23 in serum. Note that CKD data in Figure 2D showed the elevated P level up to 6 mg/dl, while the higher bound of the P level was ∼2 mg/dl (Tumor Induced Osteomalacia), 3.5 ∼4 mg/dl (Fibrous Dysplasia and XLH), and 4.5 mg/dl (healthy populations).

Bottom Line: The model also predicted that the administration reduced a urinary output of phosphorous.This model-based prediction indicated that the therapeutic reduction of FGF23 by the neutralizing antibody did not reduce phosphorus burden of CKD patients and decreased the urinary phosphorous excretion.The results herein indicate that it is necessary to understand the mechanism in CKD in which the level of FGF23 is elevated without effectively regulating phosphorus.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.

ABSTRACT
The mechanism of FGF23 action in calcium/phosphorus metabolism of patients with chronic kidney disease (CKD) was studied using a mathematical model and clinical data in a public domain. We have previously built a physiological model that describes interactions of PTH, calcitriol, and FGF23 in mineral metabolism encompassing organs such as bone, intestine, kidney, and parathyroid glands. Since an elevated FGF23 level in serum is a characteristic symptom of CKD patients, we evaluate herein potential metabolic alterations in response to administration of a neutralizing antibody against FGF23. Using the parameters identified from available clinical data, we observed that a transient decrease in the FGF23 level elevated the serum concentrations of PTH, calcitriol, and phosphorus. The model also predicted that the administration reduced a urinary output of phosphorous. This model-based prediction indicated that the therapeutic reduction of FGF23 by the neutralizing antibody did not reduce phosphorus burden of CKD patients and decreased the urinary phosphorous excretion. Thus, the high FGF23 level in CKD patients was predicted to be a failure of FGF23-mediated phosphorous excretion. The results herein indicate that it is necessary to understand the mechanism in CKD in which the level of FGF23 is elevated without effectively regulating phosphorus.

No MeSH data available.


Related in: MedlinePlus