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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
The FGF23-Klotho axis and cardiac tissue Doppler imaging in pediatric chronic kidney disease-a prospective cohort
Ylva Tranæus Lindblad1,2,3, Hannes Olauson4, Georgios Vavilis5
1Division of Pediatrics, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden. ylva.tranaeus-lindblad@sll.se.
Insights
In pediatric patients with chronic kidney disease (CKD), rising Fibroblast Growth Factor-23 (FGF23) and falling Klotho levels correlate with worsening heart function, even with controlled phosphate. These factors may impact cardiovascular disease risk.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Research
- Endocrinology
Background:
- Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is prevalent in pediatric kidney disease patients.
- CKD-MBD is a risk factor for future cardiovascular disease (CVD).
- Fibroblast growth factor-23 (FGF23) and Klotho are key players in CKD-MBD and potentially CVD development.
Purpose of the Study:
- To assess longitudinal patterns and predictors of FGF23 and Klotho in pediatric CKD and kidney transplant (CKD-T) patients.
- To investigate the associations of FGF23 and Klotho with cardiac remodeling and function.
Main Methods:
- Prospective cohort study of 74 pediatric patients (31 CKD, 43 CKD-T) followed for 3 years.
- Annual assessment of FGF23 and Klotho levels.
- Echocardiographic evaluation including pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI) for cardiac function and remodeling.
Main Results:
- High FGF23 levels were observed in 60% of CKD and 42% of CKD-T patients, despite normal Klotho and low hyperphosphatemia prevalence.
- Low GFR predicted higher FGF23 levels during follow-up.
- High FGF23 and low Klotho were associated with worse left ventricular diastolic function in CKD-T patients.
Conclusions:
- FGF23 levels increase and Klotho levels decrease with renal failure progression in pediatric CKD and CKD-T patients, irrespective of phosphate control.
- Elevated FGF23 and reduced Klotho are linked to impaired left ventricular diastolic function.
- Further research is needed to clarify the role of FGF23 and Klotho in pediatric CKD-related cardiac morbidity.
Background:
Chronic kidney disease-associated 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 has been suggested to be involved in the development of CVD.
Methods:
This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m2) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m2) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using 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 follow-up in CKD and CKD-T patients (β = -0.2, p < 0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (β = 1.8, p = 0.06). In addition, high log FGF23 (β = -0.43, p = 0.01) and low log Klotho (β = 0.44, p = 0.006) 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, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels 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.
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