Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Portale, Anthony A.; Wolf, Myles; Messinger, Shari; Perwad, Farzana; Jüppner, Harald; Warady, Bradley A.; Furth, Susan L.; Salusky, Isidro B.

doi:10.2215/cjn.02110216

Cited by 71 publications

(56 citation statements)

References 49 publications

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“…Elevations in PTH may increase cytosolic calcium in the tubules and contribute to the pathogenesis of nephrocalcinosis (44, 73, 99). Observational studies have shown associations between elevated FGF23 levels and an increased risk of CKD progression (51, 106, 128, 141). Whether FGF23 is merely a strong risk marker or has a direct role in renal injury through a yet unknown mechanism is unclear.…”

Section: Fgf23 and Pth: Potential Mediators Of Adverse Effects Of Higmentioning

confidence: 99%

Dietary Phosphorus Intake and the Kidney

Chang

Anderson

2017

Annu. Rev. Nutr.

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Although phosphorus is an essential nutrient required for multiple physiological functions, recent research raises concerns that high phosphorus intake could have detrimental effects on health. Phosphorus is abundant in the food supply of developed countries, occurring naturally in protein-rich foods and as an additive in processed foods. High phosphorus intake can cause vascular and renal calcification, renal tubular injury, and premature death in multiple animal models. Small studies in human suggest that high phosphorus intake may result in positive phosphorus balance and correlate with renal calcification and albuminuria. Although serum phosphorus is strongly associated with cardiovascular disease, progression of kidney disease, and death, limited data exist linking high phosphorus intake directly to adverse clinical outcomes. Further prospective studies are needed to determine whether phosphorus intake is a modifiable risk factor for kidney disease.

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Section: Fgf23 and Pth: Potential Mediators Of Adverse Effects Of Higmentioning

confidence: 99%

Dietary Phosphorus Intake and the Kidney

Chang

Anderson

2017

Annu. Rev. Nutr.

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“…FGF23 is a powerful risk factor for cardiovascular events and all-cause mortality across the spectrum of CKD (10)(11)(12)(13)(14). Few studies (15,16) in adults and one in children (17) have reported an independent association between higher FGF23 concentrations and incidence and progression of kidney disease in patients with an eGFR$60 ml/min per 1.73 m 2 . Another study found no association between FGF23 and risk of incident CKD in patients with type 2 diabetes (18).…”

Section: Introductionmentioning

confidence: 99%

“…Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. 18 16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) 20 18 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) 20 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)…”

Section: Introductionunclassified

Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease

Chonchol¹,

Gitomer²,

Isakova³

et al. 2017

CJASN

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“…Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism due to CKD manifested by abnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism; abnormalities of bone turnover, mineralization, volume, linear growth, or strength; and vascular or other soft tissue calcification [1, 2]. Secondary hyperparathyroidism (SHPT) develops in the course of CKD, and its prevalence and severity increase as CKD progresses towards end-stage renal disease (ESRD) [3–7].…”

Section: Introductionmentioning

confidence: 99%

An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis

et al. 2018

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BackgroundCalcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects.MethodsIn this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing.ResultsMedian plasma cinacalcet tmax was 1 h (range 0.5–4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12–72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults.ConclusionsIn conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged < 6 years.

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Fibroblast Growth Factor 23 and Risk of CKD Progression in Children

Abstract: High plasma FGF23 is an independent risk factor for CKD progression in children.

Cited by 71 publications

References 49 publications

Dietary Phosphorus Intake and the Kidney

Dietary Phosphorus Intake and the Kidney

Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease

An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis

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