scholarly journals Fibroblast growth factor 23 and cognitive impairment: The health, aging, and body composition study

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243872
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael Shlipak ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Body Composition Study ◽  
Composition Study ◽  
Fgf 23

Background Concentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue. Methods In the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho. Results The mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2. Conclusion Intact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults.

scholarly journals Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline

2018 ◽  
Vol 47 (4) ◽  
pp. 242-250 ◽  
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
...  
Keyword(s):  
Older Adults ◽  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Community Dwelling ◽  
Fibroblast Growth ◽  
Fgf 23 ◽  
Kidney Function Decline

Background: Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Methods: Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. Results: The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82–1.19] for ≥30% decline and OR 1.17 [95% CI 1.00–1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91–1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02–1.58] for highest vs. lowest quartile). Conclusion: Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults.

scholarly journals Plasma Soluble αKlotho, Serum Fibroblast Growth Factor 23, and Mobility Disability in Community-Dwelling Older Adults

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Michelle Shardell ◽  
David A Drew ◽  
Richard D Semba ◽  
Tamara B Harris ◽  
Peggy M Cawthon ◽  
...  
Keyword(s):  
Older Adults ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Community Dwelling ◽  
Fibroblast Growth ◽  
Mobility Disability ◽  
Body Composition Study ◽  
Health Aging ◽  
Community Dwelling Older Adults

Abstract Context αKlotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high FGF23 occur in chronic kidney disease (CKD). Objective We aimed to assess the relationships of αKlotho and FGF23 with mobility disability in community-dwelling older adults. Design and Setting We estimated associations of plasma-soluble αKlotho and serum FGF23 concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD. Participants Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit. Main Outcome Measures Walking disability and stair climb disability were defined as self-reported “a lot of difficulty” or an inability to walk a quarter mile and climb 10 stairs, respectively. Results Median (interquartile range [IQR]) serum FGF23 and plasma soluble αKlotho concentrations were 46.6 (36.7, 60.2) pg/mL and 630.4 (478.4, 816.0) pg/mL, respectively. After adjustment, higher αKlotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile = 0.74; 95% confidence interval l [CI] = 0.62, 0.89; P = 0.003). Higher FGF23 concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile = 1.24; 95%CI = 1.03, 1.50; P = 0.005). Overall, higher αKlotho combined with lower FGF23 was associated with the lowest walking disability rates (P for interaction = 0.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant (P for interaction &gt; 0.10). Conclusions Higher plasma soluble αKlotho and lower serum FGF23 concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD.

scholarly journals Increased Levels of sRAGE in Diabetic CKD-G5D Patients: A Potential Protective Mechanism against AGE-Related Upregulation of Fibroblast Growth Factor 23 and Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Dozio ◽  
Valentina Corradi ◽  
Elena Vianello ◽  
Elisa Scalzotto ◽  
Massimo de Cal ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cardiac Remodeling ◽  
Glycated Albumin ◽  
Fibroblast Growth Factor 23 ◽  
Protective Mechanism ◽  
Fibroblast Growth ◽  
Increased Risk ◽  
Fgf 23

Advanced glycation end products (AGEs) may induce cardiac remodeling in kidney disease by promoting fibroblast growth factor 23 (FGF-23) expression. Since AGEs are increased in diabetes mellitus (DM), our first aim was to evaluate the existence of any potential association between AGEs, FGF-23, inflammation, and increased cardiovascular risk in DM patients on dialysis (CKD-G5D). Secondarily, we explored the potential role of the soluble receptor for AGEs (sRAGE) as a marker of heart failure. Levels of glycated albumin (GA), sRAGE, c-terminal FGF-23 (cFGF-23), brain natriuretic peptide (BNP), and inflammatory mediators were compared between DM and non-DM CKD-G5D patients. The levels of sRAGE, cFGF-23, BNP, and proinflammatory markers were over the ranges of normality in both DM and non-DM groups. Only GA and sRAGE levels were increased in DM compared to non-DM patients. Plasma levels of sRAGE and CRP were the only independent predictors of BNP concentration. In conclusion, in DM CKD-G5D patients, sRAGE appeared to be a marker of cardiac remodeling. Indeed, its increase could be a potential protective mechanism against the increased risk of cardiovascular complications related to AGEs and inflammation. The causal relationship between sRAGE and cardiovascular risk in these patients needs to be further confirmed by mechanistic studies.

scholarly journals MP594THE RELATIONSHIP BETWEEN FIBROBLAST GROWTH FACTOR-23 (FGF-23) AND SELECTED CLINICAL AND LABORATORY PARAMETERS

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii648-iii649
Author(s):  
Danuta Fedak ◽  
Marek Kużniewski ◽  
Marcin Krzanowski ◽  
Paulina Dumnicka ◽  
Wladyslaw Sulowicz
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Laboratory Parameters ◽  
Fgf 23

scholarly journals Fibroblast Growth Factor 23 and Blood Pressure in Older Adults

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 236-243
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Antihypertensive Medications ◽  
Incident Hypertension ◽  
Blood Pressures ◽  
The Mean ◽  
Fgf 23

FGF-23 (fibroblast growth factor 23) regulates phosphorus and vitamin D. Elevated FGF-23 is associated with incident hypertension in young- and middle-aged adults, but there is limited data in older adults. Serum FGF-23 was measured using an intact ELISA assay in 2496 participants of the Healthy Aging and Body Composition Study. The association between FGF-23 and prevalent hypertension (self-reported and confirmed by use of antihypertensive medications) and number of antihypertensive medications was determined. The associations between FGF-23 and incident hypertension, and diastolic and systolic blood pressure trajectories were evaluated over 10 years. Models were adjusted for demographics, estimated glomerular filtration rate and albuminuria, cardiovascular disease risk factors, and measures of mineral metabolism. The mean (SD) age was 75 (3) years, with 51% women, and 40% black participants. The prevalence of hypertension at baseline was 75% and the mean systolic and diastolic blood pressures were 134 (21) mm Hg and 70 (12) mm Hg, respectively. The majority of participants without hypertension at baseline developed incident hypertension (576 of 1109 or 52%). In adjusted models, each 2-fold higher FGF-23 was associated with prevalent baseline hypertension (odds ratio=1.46 [1.24–1.73]) and greater number of blood pressure medications (IRR=1.14 [1.08–1.21]) but not with baseline diastolic or systolic blood pressure. In fully adjusted longitudinal analyses, a 2-fold higher FGF-23 was associated with incident hypertension (hazard ratio=1.18 [1.03–1.36]) and worsening systolic blood pressures (β=0.24 [0.08–0.40] mm Hg per year increase), but not with diastolic blood pressures (β=0.04 [−0.04 to 0.12] mm Hg per year increase). Higher FGF-23 concentrations are associated with prevalent and incident hypertension as well as rising systolic blood pressures in community-living older adults.

Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men

2011 ◽  
Vol 26 (4) ◽  
pp. 857-864 ◽  
Author(s):  
Majd AI Mirza ◽  
Magnus K Karlsson ◽  
Dan Mellström ◽  
Eric Orwoll ◽  
Claes Ohlsson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fracture Risk ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Elderly Men ◽  
Fgf 23

scholarly journals Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia

Medicina ◽  
2020 ◽  
Vol 56 (1) ◽  
pp. 34
Author(s):  
Cornelia Then ◽  
Evelyn Asbach ◽  
Harald Bartsch ◽  
Niklas Thon ◽  
Christian Betz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Olfactory Neuroblastoma ◽  
Mesenchymal Tumor ◽  
Fibroblast Growth ◽  
Phosphaturic Mesenchymal Tumor ◽  
Oncogenic Osteomalacia ◽  
Pet Ct ◽  
Fgf 23

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

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