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Plasma FGF23 is associated with left atrial remodeling in children on hemodialysis

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Abstract

Background

FGF23 mediates cardiac fibrosis through the activation of pro-fibrotic factors in in vitro models and is markedly elevated in kidney disease. Left atrial global longitudinal strain (LA GLS) derived by echocardiographic speckle-tracking measures longitudinal shortening of the LA walls, quantifies atrial performance and may enable detection of early LA remodeling in the setting of normal ventricular function. We hypothesized that LA GLS is abnormal in children on hemodialysis (HD) compared to healthy controls of comparable age/sex distribution and that, among HD patients, greater FGF23 levels are associated with abnormal LA GLS.

Methods

Clinical and echocardiographic data from 29 children receiving HD and 13 healthy controls were collected in a cross-sectional single-center study. Plasma FGF23 concentrations were measured using ELISA. The primary outcome was LA GLS measured using 2D speckle-tracking strain analysis. Linear regression analysis was used to investigate predictors of LA GLS in HD.

Results

Median dialysis vintage was 1.5 (IQR 0.5–4.3) years. Median intact FGF23 levels were substantially higher in the HD vs. control group (1206 [215, 4707] vs. 51 [43, 66.5] pg/ml; P = 0.0001), and LA GLS was 39.9% SD 11.6 vs. 32.8% SD 5.7 (P = 0.04). Among HD patients, higher FGF23 was associated with lower LA GLS (β per unit Ln-FGF23: − 2.7; 95% CI slope − 5.4, − 0.1; P = 0.04 after adjustment for age, body size, and HD vintage. FGF23 was not associated with LA phasic reservoir, conduit, or contractile strain.

Conclusions

In children on HD and preserved left ventricular ejection fraction, greater FGF23 is associated with lower LA GLS (indicative of impaired atrial performance).

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Funding

VA IK2-CX002195 (SS), NIDDK K24DK110427 (JHI), VA-MERIT I01-CX001901 (KLN), NHLBI R01HL148182 (KLN), and NIDDK U2CDK129496 (IBS).

Author information

Authors and Affiliations

  1. Division of Nephrology, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Room 6030, Los Angeles, CA, 90073, USA

    Shilpa Sharma

  2. Stritch School of Medicine, Loyola University Chicago, IL, Maywood, USA

    Nisha R. Patel

  3. Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Mark R. Hanudel & Isidro B. Salusky

  4. Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, CA, USA

    Joachim H. Ix

  5. Division of Cardiology, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Kim-Lien Nguyen

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  1. Shilpa Sharma
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  2. Nisha R. Patel
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  3. Mark R. Hanudel
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  4. Joachim H. Ix
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  5. Isidro B. Salusky
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  6. Kim-Lien Nguyen
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Contributions

Research idea and study design: SS, JHI, IBS, and KLN; data acquisition: IBS, MRH, NRP, SS, and KLN; data analysis/interpretation: NRP, JHI, SS, and KLN; statistical analysis: SS and NRP; supervision or mentorship: IBS, JHI, and KLN. Each author contributed important intellectual content during manuscript drafting or revision and agreed to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate.

Corresponding author

Correspondence to Shilpa Sharma.

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Conflict of interest

Dr. Ix is the principal investigator of an investigator-initiated research grant from Baxter International, serves as a data safety monitoring board member for Sanifit International, and has served on advisory boards for Alpha Young, AstraZeneca, Ardelyx Inc., and Jnana Inc. Dr. Salusky has served on advisory boards for Akebia, Inozyme, and Ardelyx. The remaining authors have declared no relevant conflicts of interest.

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Sharma, S., Patel, N.R., Hanudel, M.R. et al. Plasma FGF23 is associated with left atrial remodeling in children on hemodialysis. Pediatr Nephrol 38, 2179–2187 (2023). https://doi.org/10.1007/s00467-022-05812-x

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