EFFECT OF FGF23 AND PARICALCITOL TREATMEMT IN YOUNG HEMODIALYSIS PATIENTS WITH DIASTOLIC DYSFUNCTION

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https://storage.unitedwebnetwork.com/files/1099/d0070db83456778d8eca0057dd01bd3a.pdf

Abstract Title

First Name *

Wacharee

Last Name *

Seeherunvong

Co-author 1

Chryso Katsoufis Ckatsoufis@med.miami.edu University of Miami Pediatric Nephrology MIAMI

Co-author 2

Marissa DeFreitas mdefreitas@med.miami.edu University of Miami Pediatric Nephrology Miami

Co-author 3

Sethuraman Swaminathan sswami@med.miami.edu University of Miami Pediatric Cardiology MIAMI

Co-author 4

Jayanthi Chandar jchanda2@med.miami.edu University of Miami Pediatric Nephrology MIAMI

Co-author 5

Carolyn Abitbol cabitbol@med.miami.edu University of Miami Pediatric Nephrology MIAMI

Co-author 6

Michael Freundlich mfreundlich@med.miami.edu University of Miami Pediatric Nephrology MIAMI

Co-author 7

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

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Co-author 15

Introduction

Elevated fibroblast growth factor 23 (FGF23) levels have been associated with diastolic dysfunction (DD), a risk factor for mortality in chronic kidney disease (CKD). Arresting the progression of DD in hemodialysis (HD) patients remains a clinical priority, but longitudinal observations of DD are lacking in young HD patients. FGF23 promotes and paricalcitol (Pc) attenuates left ventricular hypertrophy (LVH) in uremic animals and patients with CKD. We hypothesized that Pc may attenuate DD progression in young HD patients with elevated FGF23 levels.

Methods

Longitudinal echocardiograms using M-Mode (posterior wall thickness, PWT), pulsed wave Doppler flow (E, A, and E/A ratios), and tissue Doppler velocity (e’, a’ and the e’/a’ and E/e’ ratios) were analyzed to diagnose LVH and DD in 20 prevalent young HD patients. Markers of diastolic function were reported as crude measurements and age-adjusted Z-scores derived from normative data in healthy North American children. C-terminal FGF23 levels and Pc treatment doses were tabulated for correlation and regression statistical associations with DD.

Results

Baseline and follow-up FGF23 levels (25,238 ± 30,244 and 19,153 ± 25,191 RU/ml) were not significantly different but increased in 7/20 (35%) after a follow-up of 7.1 ± 2.1 months while on parenteral Pc treatment. Elevated baseline PWT Z-scores improved at follow-up in 55% of patients. Initial diastolic function Z-scores (n=11) were significantly different from mean normal controls (all p<0.05) suggesting DD. Follow-up Z-scores of diastolic function during Pc treatment (15.6 ± 12.4 µg/week) were similar to baseline. FGF23 levels and hypertension correlated with reduced diastolic function. The Pc dose correlated with the PWT Z-score (r=-0.4, P<0.05), diastolic mitral A Z-score (r=-0.7, P<0.005) and tricuspid E/e’ Z-score (-0.5, P=0.05). The Pc dose relative to the log10FGF23 (Pc/log10FGF23 ratio) correlated with the mitral A Z-score (r=-0.7, P< 0.005; Figure) and the tricuspid e’/a’ Z-score (r=0.6, P<0.05).

Conclusions

In young HD patients, elevated FGF23 levels and hypertension contributed to DD. Treatment with Pc appeared to diminish progression of DD and improve LVH. Long term follow-up studies are needed to confirm these findings. Some of the content presented in this abstract was submitted at the American Society of Nephrology 2023.

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