ESPN 50th Annual Meeting

ESPN 2017


 
The FGF23 and Klotho axis in pediatric chronic kidney disease - a prospective cohort study
YLVA TRANAEUS LINDBLAD 1 Hannes Olauson 2 Georgios Vavilis 3 Ulf Hammar 4 Maria Herthelius 1 Jonas Axelsson 5 Peter Bárány 2

1- KAROLINSKA INSTITUTET, CLINTEC, Division of Pediatrics
2- KAROLINSKA INSTITUTET, CLINTEC, Division of Renal Medicine
3- KAROLINSKA UNIVERSITY HOSPITAL
4- KAROLINSKA INTITUTET, Unit of Biostatistics
5- KAROLINSKA INSTITUTET, Department of Medical Biochemistry and Biophysics
 
Introduction:

Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and have been suggested to be involved in the development of CVD.

Material and methods:

We prospectively analyzed 74 pediatric patients, 31 with CKD and 43 transplanted (CKD-T) patients annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and Klotho and associations to cardiac remodeling and function examined by echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI).

Results:

The prevalence of high FGF23 levels (≥95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during the follow-up in CKD and CKD-T patients (p<0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (p=0.06). In addition, high log FGF23 (p=0.008) and low log Klotho (p=0.02) over time were associated with a worse left ventricular diastolic function (cc-TDI e´/a´) in CKD-T patients.

Conclusions:

In pediatric CKD and CKD-T patients, FGF23 increase and Klotho decrease with progressing renal failure, despite well controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation.