Fibroblast Growth Factor 23 Concentrations Reflect Sex Differences in Mineral Metabolism and Growth in Early Infancy

Holmlund-Suila, Elisa; Viljakainen, Heli; Ljunggren, Östen; Hytinantti, Timo; Andersson, Sture; Mäkitie, Outi

doi:10.1159/000443988

Cited by 15 publications

(8 citation statements)

References 43 publications

(64 reference statements)

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“…The cohort presented in our study included older and more male participants compared with participants in this study, where female CKD participants were observed to have higher iFGF-23 levels compared with CKD males, providing a potential explanation for the disparity. This gender difference in FGF-23 levels is consistent with reports in both the very young [41] and adults [42, 43]. One postulation is that estradiol is a phosphaturic agent [44] and the loss of this hormone with onset of menopause may result in higher sPi levels, contributing to a compensatory increase in FGF-23.…”

Section: Discussionsupporting

confidence: 88%

Soluble klotho may be a marker of phosphate reabsorption

Tan¹,

Smith²,

Holt³

et al. 2017

Clinical Kidney Journal

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Background: Membrane-bound α-klotho functions as a co-receptor with fibroblast growth factor receptor at the renal tubule conferring specificity to fibroblast growth factor-23 (FGF-23), allowing it to inhibit tubular phosphate reabsorption at physiological concentrations. α-klotho also exists as a soluble protein. However, the complex interrelationships between soluble α-klotho (sKl), FGF-23 and phosphate reabsorption are poorly understood, with little known about the links between sKl, FGF-23 and phosphate reabsorption in chronic kidney disease (CKD). This study addresses this issue in a cohort of patients with and without CKD. Methods: We conducted a single-centre, cross-sectional study of contemporaneously obtained samples of blood and 24-h urine biochemistry along with sKl and intact FGF-23 (iFGF-23) from non–dialysis-dependent CKD patients and healthy volunteers. Pearson’s correlation coefficients were used to determine correlations between natural log-transformed (Ln) sKl and iFGF-23 with other parameters of interest. Backward multivariate analysis was undertaken to evaluate the relationship between mineral parameters. Results: One hundred and sixteen participants (77 with CKD and 39 healthy volunteers) were studied, of which 74 (63.8%) were male. The median age was 61 (interquartile range 49–71) years. Those with CKD had lower sKl (408 versus 542 pg/mL), higher iFGF-23 (94 versus 41 pg/mL), higher fractional excretion of phosphate (25.05 versus 10.98%) and lower daily urinary phosphate excretion (UPE) (24.8 versus 32.3 mmol/L) compared with healthy volunteers (all P ≤ 0.002). Age correlated inversely and estimated glomerular filtration rate (eGFR) correlated positively with phosphate reabsorption and Ln(sKl), while the opposite was seen with Ln(iFGF23). Upon multivariate analysis, eGFR, Ln(sKl) and parathyroid hormone were independently associated with phosphate reabsorption, whereas Ln(iFGF-23) was not, after adjustment for age. Conclusions: Abnormalities in phosphate regulatory pathways are disturbed early in CKD. While iFGF-23 is associated with phosphate excretion on univariate analyses, sKl demonstrates a significant association with phosphate reabsorption independent of iFGF-23, and this relationship deserves further exploration.

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Section: Discussionsupporting

confidence: 88%

Soluble klotho may be a marker of phosphate reabsorption

Tan¹,

Smith²,

Holt³

et al. 2017

Clinical Kidney Journal

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“…In small children, the regulatory mechanisms may be different, and there may be regulating factors no longer seen in adulthood. For example, among healthy 3-month old infants, we previously observed that girls presented with almost 50% higher intact FGF23 concentrations than boys (5). This was a novel finding, which is confirmed also in the current large cohort, where the difference between boys and girls at age 1 year was less marked, 8%, but still similar in direction.…”

Section: Discussionsupporting

confidence: 87%

“…Apart from regulation by phosphate, parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D), also other factors are involved (4). We previously demonstrated that intact FGF23 concentrations in early infancy (at age 3 months) differ between sexes, girls having significantly higher concentrations than boys (5).…”

Section: Introductionmentioning

confidence: 99%

Sex and Iron Modify Fibroblast Growth Factor 23 Concentration in 1-Year-Old Children

Holmlund-Suila

Enlund-Cerullo

Valkama

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Similarly, two studies have found gender related differences in FGF-23 in infants [63,64]. Considering the newest finding on the role of FGF-23 in vitamin D regulation [14], the gender differences found might be partly due to this connection.…”

Section: Discussionmentioning

confidence: 88%

Association Between the 25-Hydroxyvitamin D Status and Physical Performance in Healthy Recreational Athletes

Zeitler

Fritz²,

Smekal

et al. 2018

IJERPH

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Molecular and clinical studies have linked vitamin D (vitD) deficiency to several aspects of muscle performance. For this retrospective cross-sectional study data from 297 male (M) and 284 female (F) healthy recreational athletes were used to evaluate the prevalence of vitD deficiency in athletes living in Austria and to determine whether serum 25-hydroxyvitamin D (25(OH)D) correlates with maximal (Pmax) and submaximal physical performance (Psubmax) measured on a treadmill ergometer. The data were controlled for age, season, weekly training hours (WTH), body mass index (BMI) and smoking status. 96 M and 75 F had 25(OH)D levels ≤ 20 ng/mL. 25(OH)D levels showed seasonal variations, but no seasonal differences in Pmax and Psubmax were detected. M with 25(OH)D levels ≤ 20 ng/mL had significantly lower Psubmax (p = 0.045) than those with normal levels. In F no significant differences in Pmax or Psubmax were detected. Stepwise multiple regression analysis including all covariates revealed significant correlations between 25(OH)D levels and Pmax (β = 0.138, p = 0.003) and Psubmax (β = 0.152, p = 0.002) in M. Interestingly, for F significant correlations between 25(OH)D and both Pmax and Psubmax disappeared after adding WTH to the model. In conclusion, our data suggest that 25(OH)D status is associated with physical performance especially in M, while in F, WTH and BMI seem to affect the correlation.

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Fibroblast Growth Factor 23 Concentrations Reflect Sex Differences in Mineral Metabolism and Growth in Early Infancy

Cited by 15 publications

References 43 publications

Soluble klotho may be a marker of phosphate reabsorption

Soluble klotho may be a marker of phosphate reabsorption

Sex and Iron Modify Fibroblast Growth Factor 23 Concentration in 1-Year-Old Children

Association Between the 25-Hydroxyvitamin D Status and Physical Performance in Healthy Recreational Athletes

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