Status
Conditions
About
Despite recent progress in the field of hemodialysis (HD), mortality remains unacceptably high, particularly due to cardiac arrhythmias. Recent evidence suggests that fibroblast growth factor 23 (FGF23) is implicated in the pathogenesis of cardiac arrhythmias and sudden death. However, several aspects of both the pathogenetic mechanism(s) as well as the actual association in individuals with Chronic Kidney Disease (CKD) and the effect of dialysis clearance of FGF23 need to be elucidated.
The investigators aim at testing the independent association of FGF23 changes due to dialysis removal and electrocardiographic (ECG) abnormalities (namely QTc prolongation) in a well characterized sample of patients undergoing maintenance HD. The study will be developed in the Division of Nephrology, Ente Ospedaliero Cantonale.
Full description
This is an exploratory, observational, prospective, mono-center study that aims to elucidate the pathogenesis of cardiac repolarization and arrhythmias in subjects with CKD receiving maintenance dialysis.
This exploratory research project aims to confirm the link between FGF23 and ECG abnormalities (QTc as a proxy for cardiac arrhythmias) in a well-characterized sample of HD patients and expand our understanding of the molecular mechanisms by which FGF23 may trigger arrhythmias.
Previous works suggest that FGF23 cardiac toxicity may be mediated by the activation of FGFR4 and that modulation of FGF23-FGFR4 signaling through monoclonal antibodies can attenuate the toxic effects of FGF23 on the CM. Although these preliminary data warrant clinical and molecular confirmation, they also suggest FGF23-FGFR4 modulation as a novel potential therapeutic target in CKD to improve morbidity and mortality.
During a standard dialysis session, FGF23 is acutely removed while Ca2+ is provided to the patients. However, shortly after the HD session completion, it was documented that FGF23 serum levels rebound. The investigators hypothesize that acute reduction and subsequent rebound of circulatory levels of FGF23 coupled with calcium loading induced by HD may favour a Ca 2+ influx in the CM and trigger cardiac arrhythmias.
This exploratory study aims to determine the independent association between variations in serum levels of FGF23 and QTc (msec) during and after dialysis. In particular, the primary endpoint of the study is defined as the association between QTc variations (msec) defined as the difference between QTc pre-dialysis and QTc 1 hour after dialysis session completion and variations of serum levels of FGF23 defined as the difference between serum levels of FGF23 at dialysis session completion and after 1-hour form dialysis session completion. The investigators hypothesize that these time points should maximize the chance of detecting a significant association between the exposure variable (FGF23) and the outcome of interest (QTc).
All study procedures are non-invasive, and they will be carried out between the beginning of the last HD of the week and the beginning of the first HD of the following week (long interdialytic interval) to allow for the maximum variation of serum levels of FGF23 between dialysis sessions.
All study-related procedures are performed on top of standard clinical practice, and guidelines are performed non-invasively. Study participants will undergo the following procedures:
Adverse event: The occurrence of any adverse events (AE) will be recorded for the occurrence of any event from study inception until the end of the following week This exploratory study will be carried out at the Division of Nephrology, Ente Ospedaliero Cantonale (EOC), Ticino, Switzerland.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
The study envisages the enrolment of:
Exclusion Criteria:
30 participants in 1 patient group
Loading...
Central trial contact
Antonio Bellasi, MD, PhD; Davide Salera, MD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal