2019
DOI: 10.3390/toxins11110647
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FGF23 and Phosphate–Cardiovascular Toxins in CKD

Abstract: Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, F… Show more

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Cited by 59 publications
(52 citation statements)
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“…The FGF23 directly targets proximal tubules to increase phosphate excretion by downregulating the cell surface expression of the sodium-dependent phosphate transporters in the proximal tubule. The FGF23 lowers serum phosphorus concentrations by the suppression of phosphorus reabsorption in proximal tubules and by active vitamin D reduction through 1α-hydroxylase suppression (31)(32)(33). In this study FGF23 was not detected in diabetic mice or in healthy mice administered P. gingivalis LPS (Fig.…”
Section: Expression Of Renal Physiologically Active Molecules In Diabmentioning
confidence: 51%
See 1 more Smart Citation
“…The FGF23 directly targets proximal tubules to increase phosphate excretion by downregulating the cell surface expression of the sodium-dependent phosphate transporters in the proximal tubule. The FGF23 lowers serum phosphorus concentrations by the suppression of phosphorus reabsorption in proximal tubules and by active vitamin D reduction through 1α-hydroxylase suppression (31)(32)(33). In this study FGF23 was not detected in diabetic mice or in healthy mice administered P. gingivalis LPS (Fig.…”
Section: Expression Of Renal Physiologically Active Molecules In Diabmentioning
confidence: 51%
“…Osteocyte-derived hormone broblast growth factor (FGF) 23 acts as a key regulator of the renal phosphate metabolism which reduces renal phosphate uptake. In chronic kidney disease serum FGF23 levels are massively elevated (31)(32)(33). Angiotensin-converting enzyme 2 (ACE2), a monocarboxypeptidase that cleaves a typical renal pressor hormone angiotensin (Ang) into Ang 1-7 and degrades Ang I to Ang 1-9, is expressed in proximal tubular epithelial cells, and increases in diabetic kidney and hypertensive renal diseases (34,35).…”
Section: Introductionmentioning
confidence: 99%
“…Moreover, the clinical significance of correcting serum PTH concentrations does not seem to be clearly shown, and therefore measurements of serum intact PTH concentrations in general population need to be evaluated further in the future. Fibroblast growth factor-23 (FGF23), which is produced predominantly by osteoblasts and osteocytes, regulates renal tubular phosphate reabsorption, acts as a counter-regulatory hormone of active vitamin D, increases as a consequence of a decreased GFR, and thus plays a pivotal role in CKD-MBD (37,38). Since serum FGF23 concentrations can be a better indicator representing pathological background of CKD-MBD than serum PTH concentrations, using serum FGF23 concentration instead of serum PTH concentrations as the dependent variable may provide more definitive results.…”
Section: Discussionmentioning
confidence: 99%
“…In Japan, a serum 25(OH)VitD3 concentration <20 ng/ml was set as the threshold by major academic societies such as the Japan Endocrine Society (JES) (39). However, the JES also set a serum 25(OH)VitD3 concentration <15 ng/ml to be suggestive of the diagnosis of hypocalcemia due to vitamin D deficiency (38). Further, the Pediatric Endocrine Society recommends a serum 25(OH)VitD3 concentrations of <20 ng/ml and <15 ng/ml for the thresholds to define vitamin D insufficiency and deficiency, respectively (40).…”
Section: Discussionmentioning
confidence: 99%
“…FGF23 concentrations rise 1000-fold above normal values in order to keep the phosphate levels within the normal range and are associated with disease progression [137]. In ESRD, FGF23 fails to sustain phosphate homeostasis and hyperphosphatemia and increased FGF23 levels stimulate the development of hypertension, vascular calcification, and left ventricular hypertrophy [138]. In CKD patients, there is a dose-dependent association between circulating FGF23 levels and an increased risk of premature mortality [139,140].…”
Section: Vitamin D Fibroblast Growth Factor 23 and Parathyroid Hormonementioning
confidence: 99%