Fibroblast Growth Factor 23 and Risk of Cardiac Arrhythmias in Hemodialysis Patients

NCT06668831 | Recruiting

• 1 other identifier: FibCA-HD
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hemodialysis

Keywords

fgf23; cardiac arrhythmia; QTc; cardiovascular risk

Outcome Measures

Primary Outcomes (1)

• Associations of QTc and FGF23 changes

  The primary endpoint of the study is defined as the association between QTc variations (msec) defined as a continuous variable as the difference between QTc pre-dialysis and QTc 1 hour after dialysis session completion and variations of serum levels of FGF23 defined as a continuous variable as the difference between serum levels of FGF23 at dialysis session completion and after 1-hour form dialysis session completion. We 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).

  the primary endpoint will be assessed one hour after dialysis cessation

Secondary Outcomes (2)

• To gauge the dynamic association between FGF23 and QTc we will also explore

  these endpoints will be assessed between dialysis session initiation and 1 hour after dialysis session cessation

• To gauge the dynamic association between FGF23 and QTc we will also explore

  These endpoints will be assessed bewteen the beginning of the last dialysis of the week and the beginning of the first dialysis of the following week (72 hours)

Study Arms (1)

Subjects on maintenance hemodialysis

The study envisages the enrolment of: * adult subjects (\>18 years of age) who are able to sign an informed consent. * on maintenance HD (for at least 3 months) * without history of cardiac arrhythmias at study recruitment define as atrial fibrillation or pace-maker assisted cardiac rhythm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult subjects on maintenance hemodialysis

You may not qualify if:

• history of cardiac arrhythmias at study recruitment define as atrial fibrillation or pace-maker assisted cardiac rhythm

Sponsors & Collaborators

• Antonio Bellasi: lead

Study Sites (1)

Servizio di Nefrologia, Ospedale Regionale di Lugano, Civico

Lugano, CH-6903, Switzerland

RECRUITING

Related Publications (10)

• Arrigo M, Von Moos S, Gerritsen K, Sadoune M, Tangvoraphonkchai K, Davenport A, Mebazaa A, Segerer S, Cippa PE. Soluble CD146 and B-type natriuretic peptide dissect overhydration into functional components of prognostic relevance in haemodialysis patients. Nephrol Dial Transplant. 2018 Nov 1;33(11):2035-2042. doi: 10.1093/ndt/gfy113.

  PMID: 29733422 BACKGROUND

• Tiong MK, Krishnasamy R, Smith ER, Hutchison CA, Ryan EG, Pascoe EM, Hawley CM, Hewitson TD, Jardine MJ, Roberts MA, Cho Y, Wong MG, Heath A, Nelson CL, Sen S, Mount PF, Vergara LA, Paul-Brent PA, Johnson DW, Toussaint ND. Effect of a medium cut-off dialyzer on protein-bound uremic toxins and mineral metabolism markers in patients on hemodialysis. Hemodial Int. 2021 Jul;25(3):322-332. doi: 10.1111/hdi.12924. Epub 2021 Mar 28.

  PMID: 33779046 BACKGROUND

• Fu X, Cui QQ, Ning JP, Fu SS, Liao XH. High-Flux Hemodialysis Benefits Hemodialysis Patients by Reducing Serum FGF-23 Levels and Reducing Vascular Calcification. Med Sci Monit. 2015 Nov 11;21:3467-73. doi: 10.12659/msm.894894.

  PMID: 26558428 BACKGROUND

• Sikaneta T, Ho N, Bellasi A, Mahdavi S, Taskapan H, Svendrovski A, Makanjee B, Roberts J, Wu G, Nathoo B, Tam P. QTc Interval Prolongation Is Independently Associated with FGF23 and Predicts Mortality in Predialysis Chronic Kidney Disease. Cardiorenal Med. 2024;14(1):45-57. doi: 10.1159/000535133. Epub 2024 Jan 8.

  PMID: 37963445 BACKGROUND

• Graves JM, Vallejo JA, Hamill CS, Wang D, Ahuja R, Patel S, Faul C, Wacker MJ. Fibroblast growth factor 23 (FGF23) induces ventricular arrhythmias and prolongs QTc interval in mice in an FGF receptor 4-dependent manner. Am J Physiol Heart Circ Physiol. 2021 Jun 1;320(6):H2283-H2294. doi: 10.1152/ajpheart.00798.2020. Epub 2021 Apr 30.

  PMID: 33929896 BACKGROUND

• Di Iorio B, Bellasi A. QT interval in CKD and haemodialysis patients. Clin Kidney J. 2013 Apr;6(2):137-43. doi: 10.1093/ckj/sfs183. Epub 2013 Jan 17.

  PMID: 26019841 BACKGROUND

• Vazquez-Sanchez S, Poveda J, Navarro-Garcia JA, Gonzalez-Lafuente L, Rodriguez-Sanchez E, Ruilope LM, Ruiz-Hurtado G. An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk. Front Physiol. 2021 Mar 9;12:632260. doi: 10.3389/fphys.2021.632260. eCollection 2021.

  PMID: 33767635 BACKGROUND

• Niu J, Shah MK, Perez JJ, Airy M, Navaneethan SD, Turakhia MP, Chang TI, Winkelmayer WC. Dialysis Modality and Incident Atrial Fibrillation in Older Patients With ESRD. Am J Kidney Dis. 2019 Mar;73(3):324-331. doi: 10.1053/j.ajkd.2018.09.011. Epub 2018 Nov 16.

  PMID: 30449517 BACKGROUND

• Rantanen JM, Riahi S, Schmidt EB, Johansen MB, Sogaard P, Christensen JH. Arrhythmias in Patients on Maintenance Dialysis: A Cross-sectional Study. Am J Kidney Dis. 2020 Feb;75(2):214-224. doi: 10.1053/j.ajkd.2019.06.012. Epub 2019 Sep 18.

  PMID: 31542235 BACKGROUND

• Di Lullo L, Rivera R, Barbera V, Bellasi A, Cozzolino M, Russo D, De Pascalis A, Banerjee D, Floccari F, Ronco C. Sudden cardiac death and chronic kidney disease: From pathophysiology to treatment strategies. Int J Cardiol. 2016 Aug 15;217:16-27. doi: 10.1016/j.ijcard.2016.04.170. Epub 2016 May 3.

  PMID: 27174593 BACKGROUND

Related Links

• STROBE statement
• Declaration of Helsinki
• Ordinance on Human Research with the Exception of Clinical trials (HRO)
• Human Research Act (HRA)

Biospecimen

Retention: SAMPLES WITHOUT DNA

All study biological materials (serum sample) will be stored in the EOC biobank

MeSH Terms

Conditions

Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antonio Bellasi, MD, PhD

  Ente Ospedaliero Cantonale, Bellinzona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Bellasi, MD, PhD

CONTACT

+410918117119; antonio.bellasi@eoc.ch

Davide Salera, MD

CONTACT

+410918116166; davide.salera@eoc.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Nephrology Consultant and Principal Investigator

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: October 31, 2024
• Study Start: October 12, 2024
• Primary Completion: October 31, 2025
• Study Completion: December 30, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-07

Locations

CH (1)