Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men

Antoniucci, Diana M.; Yamashita, Takefumi; Portale, Anthony A.

doi:10.1210/jc.2006-0021

Cited by 386 publications

(307 citation statements)

References 43 publications

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“…In this study, as well as in a recently published large cohort of adults with predialysis CKD (9), circulating FGF-23 levels were already elevated in stage 2 CKD, consistent with the marked upregulation of FGF-23 expression in bone observed in patients with this degree of kidney disease (18). Although controversial (19)(20)(21), some investigators have shown that FGF-23 levels increase in response to oral phosphate loading in healthy volunteers (22) as well as in wild-type and CKD rats (23); thus, an increased, possibly intermittent, phosphate burden in the context of even mildly decreased renal function may contribute to enhanced FGF-23 secretion. Phosphate-independent mechanisms, such as subtle, subclinical elevations in PTH, may also contribute to the increase in FGF-23 levels in CKD.…”

Section: Discussionsupporting

confidence: 88%

Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease

Wesseling‐Perry

Pereira

Tseng

et al. 2012

Clinical Journal of the American Society of Nephrology

146

124

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SummaryBackground and objectives The relationship between parathyroid hormone, fibroblast growth factor 23 (FGF-23), and indices of bone turnover and mineralization in children with early CKD is unknown; thus, this study characterizes the features of renal osteodystrophy and their relationship to biochemical markers of mineral metabolism.Design, setting, participants, & measurements Fifty-two patients 2-21 years of age with predialysis CKD underwent tetracycline-labeled bone biopsy. Anthropomorphic measurements and biochemical values were obtained at the time of biopsy.Results Serum phosphorus levels were increased in 4% of patients with stage 3 CKD and 43% of those with stage 4/5 CKD. Parathyroid hormone concentrations were elevated in 36% of patients with stage 2, 71% with stage 3, and 93% with stage 4/5 CKD, whereas FGF-23 values were elevated in 81% of all patients, regardless of CKD stage. Bone turnover was normal in all patients with stage 2, but was increased in 13% with stage 3 and 29% with stage 4/5 CKD. Defective mineralization was present in 29% of patients with stage 2, 42% with stage 3, and 79% with stage 4/5 CKD. Defective skeletal mineralization was associated with lower serum calcium levels and increased parathyroid hormone concentrations.Conclusions Elevated circulating FGF-23 levels and defects in skeletal mineralization early in the course of CKD suggest that factors other than the traditional markers of mineral deficiency play a crucial role in the development of renal bone disease.

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Section: Discussionsupporting

confidence: 88%

Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease

Wesseling‐Perry

Pereira

Tseng

et al. 2012

Clinical Journal of the American Society of Nephrology

146

124

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“…Epidemiologic and experimental data support FGF23 elevation as a novel risk factor for ESRD, cardiovascular disease, and mortality (2)(3)(4)(5). These findings, along with evidence that FGF23 levels increase with dietary phosphate loading and decrease with restriction (6)(7)(8), have stimulated interest in developing clinical strategies to reduce FGF23 levels in CKD.…”

Section: Introductionmentioning

confidence: 96%

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Isakova

Barchi-Chung

Enfield

et al. 2013

Clinical Journal of the American Society of Nephrology

133

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SummaryBackground Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited.Design, setting, participants, & measurements In this 232 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline.Results Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet 3 time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC 3 time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet 3 LC 3 time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. ConclusionThe combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 324 and normal serum phosphate levels.

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“…Previous studies on FGF23 response on phosphate loading have revealed conflicting results because of differences in timing of sample collection, follow-up, and different assays used to determine FGF23 levels (2)(3)(4)(5). One study demonstrated an increase in C-terminal FGF23 (cFGF23) on phosphate loading, but it measured FGF23 only after 5 days, thereby precluding any conclusion on the time window before that (3).…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Phosphate and Calcium Intake on Fibroblast Growth Factor-23

Vervloet

Ittersum²,

Büttler³

et al. 2011

Clinical Journal of the American Society of Nephrology

195

133

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SummaryBackground and objectives Little is known about the influence of dietary phosphate intake on fibroblast growth factor-23 (FGF23) and its subsequent effects on vitamin D levels. This study addresses changes in intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23), phosphaturia, and levels of vitamin D on high and low phosphate and calcium intake.Design, setting, participants, & measurements Ten healthy subjects adhered to a diet low or high in phosphate and calcium content for 36 hours each with a 1-week interval during which subjects adhered to their usual diet. Serum phosphate, calcium, vitamin D metabolites, parathyroid hormone (PTH), and FGF23 levels (cFGF23 and iFGF23) were measured several times a day. Phosphate, calcium, and creatinine excretion was measured in 24-hour urine on all study days.Results Serum phosphate levels and urinary phosphate increased during high dietary phosphate intake (from 1.11 to 1.32 mmol/L, P Ͻ 0.0001 and 21.6 to 28.8 mmol/d, P ϭ 0.0005, respectively). FGF23 serum levels increased during high dietary phosphate/calcium intake (cFGF23 from 60 to 72 RU/ml, P Ͻ 0.001; iFGF23 from 33 to 37 ng/L, P ϭ 0.003), whereas PTH declined. 1,25-Dihydroxyvitamin D (1,25D) showed an inverse relation with FGF23.Conclusions Variation in dietary phosphate and calcium intake induces changes in FGF23 (on top of a circadian rhythm) and 1,25D blood levels as well as in urinary phosphate excretion. These changes are detectable the day after the change in the phosphate content of meals. Higher FGF23 levels are associated with phosphaturia and a decline in 1,25D levels.

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Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men

Abstract: We conclude that in healthy men, changes in dietary phosphorus within the physiological range of intakes regulate serum FGF-23 concentrations and suggest that dietary phosphorus regulation of 1,25(OH)(2)D production is mediated, at least in part, by changes in circulating FGF-23.

Cited by 386 publications

References 43 publications

Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease

Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Effects of Dietary Phosphate and Calcium Intake on Fibroblast Growth Factor-23

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