Relationship Of Fibroblast Growth Factor 23 Research Articles

Intact and C-Terminal FGF23 Assays-Do Kidney Function, Inflammation, and Low Iron Influence Relationships With Outcomes?

Higher fibroblast growth factor-23 (FGF23) concentrations are associated with heart failure and mortality in diverse populations, but the strengths of associations differ markedly depending up on which assay is used. We sought to evaluate whether iron deficiency, inflammation, or kidney function account for differences in the strengths of associations between these 2 FGF23 assays with clinical outcomes. Case cohort study from the Cardiovascular Health Study. A total of 844 community-dwelling individuals aged 65 years or older with and without chronic kidney disease were followed for 10 years. Outcomes included death, incident heart failure (HF), and incident myocardial infarction (MI). Exposure was baseline intact and C-terminal FGF23. Using modified Cox models, adjusting sequentially we tested whether observed associations of each assay with outcomes were attenuated by iron status, inflammation, kidney function, or their combinations. FGF23 measured by either assay was associated with mortality in unadjusted analysis (intact FGF23 hazard ratio [HR] per 2-fold higher 1.45; 95% CI, 1.25-1.68; C-terminal FGF23 HR 1.38; 95% CI, 1.26-1.50). Adjustment for kidney function completely attenuated associations of intact FGF23 with mortality (HR 1.00; 95% CI, 0.85-1.17), but had much less influence on the association of C-terminal FGF23, for which results remained significant after adjustment (HR 1.15; 95% CI, 1.04-1.28). Attenuation was much less with adjustment for iron status or inflammation. Results were similar for the HF end point. Neither C-terminal or intact FGF23 was associated with MI risk. The relationship of FGF23 with clinical end points is markedly different depending on the type of FGF23 assay used. The associations of biologically active FGF23 with clinical end points may be confounded by kidney disease, and thus much weaker than previously thought.

Fibroblast growth factor 23 levels decline following sleeve gastrectomy.

Levels of fibroblast growth factor 23 (FGF23) have been positively associated with measures of adiposity, cardiovascular disease and mortality. It is unclear whether the relationship of FGF23 with cardiovascular disease and mortality is confounded by obesity. We aimed to determine whether FGF23 concentrations decline following a reduction in adiposity after sleeve gastrectomy (SG). The effect of SG on FGF23 was evaluated in 22 obese adults (59% male) with type 2 diabetes. Fat mass, weight, BMI, plasma intact FGF23, parathyroid hormone (PTH) and leptin were determined at baseline and at 12months following SG. At baseline, median (IQR) age was 51 (43-54) years, fat mass 47.8 (41.0-59.4)kg, BMI 40.9 (36.9-46.9)kg/m2 and FGF23 66.2 (55.3-82.9)pg/mL. Significant changes in median BMI (-10.8kg/m2 , 95% CI: -12.9 to -7.2, P<0.0001), fat mass (-20.0kg, 95% CI: -26.7 to -12.4, P<0.0001) and weight (-34.7kg, 95% CI -40.0 to -23.1, P<0.0001) were observed after SG. FGF23 (-12.4pg/mL, 95% CI: -19.5 to 2.0, P=0.005), PTH (-1.1pmol/L, 95% CI: -1.7 to 0.2, P=0.009) and leptin (-1687pg/mL, 95% CI -4524 to -563, P=0.01) declined following SG. Change in FGF23 was not significantly associated with change in measures of adiposity, PTH or leptin. FGF23 concentrations decline in the setting of significant weight loss following SG, implying that increased FGF23 concentrations are a downstream consequence of obesity, which may confound its association with cardiometabolic dysfunction. Mediators of the relationship between adiposity and FGF23 require further elucidation.

Fibroblast growth factor 23 and renal function among young and healthy individuals.

Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals. Healthy individuals aged 25-41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate. Multivariable regression models were constructed to assess the relationship of FGF-23 with parameters of renal function, endothelin-1 and fractional phosphate excretion. The median age of 2077 participants was 37 years, 46% were males. The mean estimated glomerular filtration rate (eGFR - CKD-EPI creatinine-cystatin C equation) and fractional phosphate excretion were 110 mL/min/1.73 m2 and 8.7%, respectively. After multivariable adjustment, there was a significant inverse relationship of FGF-23 with eGFR (β per 1 log-unit increase -3.81; 95% CI [-5.42; -2.20]; p<0.0001). Furthermore, we found a linear association between FGF-23 and endothelin-1 (β per 1 log-unit increase 0.06; [0.01, 0.11]; p=0.01). In addition, we established a significant relationship of FGF-23 with fractional phosphate excretion (β per 1 log-unit increase 0.62; [0.08, 1.16]; p=0.03). Increasing plasma FGF-23 levels are strongly associated with decreasing eGFR and increasing urinary phosphate excretion, suggesting an important role of FGF-23 in the regulation of kidney function in young and healthy adults.

Association of serum fibroblast growth factor 23 with calcium metabolism in patients with end-stage renal disease undergoing hemodialysis

Background: The association between the function of fibroblast growth factor 23 (FGF23) and different components of calcium metabolism has remained unclear in patients with renal dysfunction undergoing hemodialysis. Objectives: The present study aimed to assess the association of the level of FGF23 and calcium metabolism status in hemodialysis patients. Patients and Methods: This cross-sectional study conducted on 90 consecutive patients suffering end-stage renal disease (ESRD) who underwent hemodialysis. The serum levels of FGF23 and intact parathyroid hormone (iPTH) levels were measured using the ELISA technique. Results: The serum levels of FGF23 were directly associated with iPTH level (r = 0.251, P = 0.020) and slightly with the duration of dialysis (r = 0.203, P = 0.063). However serum FGF23 was not significantly related to other indices including levels of calcium, phosphorus, magnesium, vitamin D, albumin, and even body mass index (BMI). No difference was found in the level of FGF23 between men and women with ESRD under hemodialysis. Conclusions: In ESRD patients undergoing hemodialysis, the association of FGF23 with iPTH was detected, while there was not any relationship of FGF23 with other indices including calcium, phosphorus, and vitamin D.

Abstract P241: Fibroblast Growth Factor-23 and Death, Heart Failure, and Cardiovascular Events in Community-Living Individuals: the Cardiovascular Health Study

Background: Fibroblast growth factor-23 (FGF23) increases renal phosphorus excretion and inhibits calcitriol synthesis. In advanced chronic kidney disease (CKD), high FGF23 levels are associated with increased mortality. The relationship of FGF23 with all-cause mortality, incident heart failure (HF), and incident cardiovascular disease (CVD) in community-living populations is uncertain Methods: Among 3,107 community-living individuals aged &gt; 65 years, we measured plasma FGF23 concentrations in 1996-97. Follow-up for death and adjudicated HF and CVD events continued through 2008. Cox proportional hazards models evaluated associations of FGF23 with each outcome. We tested interactions by CKD status (eGFR &lt; 60ml/min/1.73m 2 or ACR ≥ 30mg/g). Results: During 10.5 years median follow-up, there were 1,730 deaths, 697 adjudicated incident HF events, and 797 adjudicated incident CVD events. FGF23 was elevated in persons with eGFR &lt; 80ml/min/1.73m 2 or with urine ACR &gt; 30mg/g. Although higher FGF23 concentrations were associated with death and HF o in combined analyses when adjusted for traditional CVD risk factors and kidney function (HR 1.25 [1.14, 1.36] for death, 1.41 [1.23, 1.61] for HF, and 1.12 [0.98, 1.29] for CVD), the associations were consistently stronger for those with CKD (all P interactions &lt; 0.006; Table ). Conclusions: FGF23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These relationships appear stronger in persons with CKD. Association of FGF23 with Incident Heart Failure, Cardiovascular Disease, and All-Cause Death Stratified by CKD. The Cardiovascular Health Study FGF23 Quartiles Linear model 1 2 3 4 Per Doubling of FGF23 P-value FGF23 Range (RU/mL) &lt; 51 51-70 71-100 &gt; 100 Chronic Kidney Disease (N=1,128) All-Cause Mortality Annual event rate (# events / # at risk) 7.7 (90/141) 7.6 (150/235) 8.7 (191/285) 14.3 (404/467) Adjusted * HR (95% CI) 1.00 (ref) 0.97 (0.75, 1.26) 1.09 (0.84, 1.41) 1.87 (1.47, 2.38) 1.41 (1.30, 1.52) &lt;0.001 Incident Heart Failure † Annual event rate (# events / # at risk) 3.7 (38/136) 3.8 (63/213) 4.6 (81/256) 7.7 (145/350) Adjusted * HR (95% CI) 1.00 (ref) 0.97 (0.64, 1.46) 1.16 (0.78, 1.73) 1.94 (1.32, 2.83) 1.52 (1.33, 1.72) &lt;0.001 Incident Cardiovascular Disease ‡ Annual event rate (# events / # at risk) 5.1 (39/104) 6.2 (71/156) 6.2 (76/184) 9.5 (126/257) Adjusted * HR (95% CI) 1.00 (ref) 1.09 (0.74, 1.63) 1.09 (0.73, 1.62) 1.49 (1.02, 2.18) 1.24 (1.09, 1.43) 0.002 No Chronic Kidney Disease (N=1,979) All-Cause Mortality Annual event rate (# events / # at risk) 4.3 (270/651) 4.8 (247/550) 5.0 (228/489) 5.9 (150/289) Adjusted * HR (95% CI) 1.00 (ref) 1.10 (0.93, 1.32) 1.15 (0.96, 1.38) 1.29 (1.05, 1.59) 1.07 (0.98, 1.17) 0.15 Incident Heart Failure † Annual event rate (# events / # at risk) 1.9 (109/631) 2.3 (106/531) 2.3 (91/463) 3.1 (64/256) Adjusted * HR (95% CI) 1.00 (ref) 1.19 (0.90, 1.56) 1.11 (0.84, 1.48) 1.37 (0.99, 1.89) 1.17 (1.02, 1.33) 0.023 Incident Cardiovascular Disease ‡ Annual event rate (# events / # at risk) 3.5 (149/496) 4.0 (142/431) 4.2 (129/374) 4.0 (65/204) Adjusted * HR (95% CI) 1.00 (ref) 1.12 (0.89, 1.42) 1.16 (0.91, 1.42) 1.07 (0.79, 1.45) 0.99 (0.87, 1.13) 0.899 P-values for interaction in the adjusted model were &lt; 0.001 for all cause mortality, 0.008 for incident HF, and 0.006 for incident CVD † Excludes 271 participants with prevalent HF at baseline. ‡ Excludes 901 participants with prevalent CVD at baseline * Adjusted for age, sex, race, health status (fair or poor vs. better), current smoking, prior stroke, prior MI, prior HF, prior claudication, hypertension, diabetes (nl, ifg, dm), bmi, estrogen use (women), total chol, lipid med use, natural log (CRP). Funding(This research has received full or partial funding support from the American Heart Association, National Center)