FGF23 Is Associated with Adiposity in Dialysis Patients: Crosstalk Between Bone and Adipose?

Presentation Number: SUN 338
Date of Presentation: April 2nd, 2017

Janet M. Chiang*1, George A. Kaysen2, Anne L. Schafer3 and Kirsten L. Johanesn4
1University of California, San Francisco, San Francisco, CA, 2University of California, Davis, 3Univ of California-San Francisco/San Francisco VA Med Ctr, San Francisco, CA, 4University of California, San Francisco and San Francisco VA

Abstract

FGF23 is known for its function as a phosphatonin and suppressor of 1,25-OH2 vitamin D production; its concentration rises throughout CKD and can be extremely high in patients with ESRD. Evidence suggests that FGF23 may be involved in signaling between bone and adipose, but its role is uncertain. In a study in ESRD participants, FGF23 level was inversely associated with BMI. In a study with ob/ob mice, injections of leptin led to an increase in FGF23. To probe these apparently paradoxical results, we hypothesized that FGF23 would be associated with adiposity and the association would be explained in part by leptin. We performed univariate and multivariate logistic regression analyses using data from 611 participants in the ACTIVE/ADIPOSE cohort of prevalent hemodialysis patients. Mean age was 57±14 years, 39.5% were female, and the median time on dialysis was 2.85 years. Serum FGF23 concentration was measured by C-terminal ELISA. BMI and waist circumference were measured, and percentage fat was determined by bioelectrical impedance spectroscopy as a more direct assessment of adiposity. We found FGF23 to be inversely associated with BMI in univariate analyses and after adjusting for potential confounders, including age, race, gender, calcium, phosphorus, albumin, and time on dialysis (-0.69 kg/m2 per pg/mL of FGF23, 95% CI -1.10, -0.30, p=0.001). FGF23 was also inversely associated with waist circumference (-1.20 cm, 95% CI -2.14, -0.26, p=0.01), and percentage fat (-0.01%, 95% CI -0.01, -0.003, p=0.001) in multivariate analyses. We explored the extent to which FGF23 was associated independently with visceral and non-visceral adiposity. FGF23 was not significantly associated with waist circumference after adjusting for fat mass but was inversely associated with fat mass after adjusting for waist circumference. We investigated the role of leptin in these relationships. Leptin was inversely associated with FGF23, and the association between FGF23 and BMI was attenuated when we adjusted for leptin (-0.18 kg/m2, 95% CI -0.48, 0.11, p=0.24), as was the association with waist circumference (-0.25cm, 95% CI -0.94, 0.44, p=0.48), and percentage fat (-0.002%, 95% CI -0.005, 0.002, p=0.31). We conclude that there is a negative association between FGF23 and adiposity that is mainly related to non-visceral adiposity and explained in part by leptin. This may be one mechanism through which high FGF23 levels contribute to mortality in dialysis patients given that higher fat mass is associated with better survival in this population (“obesity paradox”).

 

Nothing to Disclose: JMC, GAK, ALS, KLJ