FGF23 and Cardiovascular Damage in Anemia With an Without Chronic Kidney Disease.

NCT05356325 | Recruiting DMC

• 1 other identifier: PI20/1645
• Study Type: observational
• Target: 401
• Locations: 1 country
• Sites: 1

Brief Summary

Anemia is associated with cardiovascular disease. Iron deficiency is usually induced in chronic kidney disease (CKD). In clinical studies, an inverse association between serum levels of iron and fibroblast growth factor 23 (FGF23), a cardiovascular risk factor, has been demonstrated. In addition, a number of the I.V. iron presentations mostly used to treat anemia show unwanted side effects related to phosphate alterations and increased FGF23. Objectives. The General Objective of this project is to evaluate, through in vivo and in vitro studies, the cardiovascular alterations related to the anemia-induced increase in FGF23 production; as well as the identification of possible molecular targets that may be useful in its prevention and/or palliation. Specific Objectives are: 1) To determine in a population with anemia (due to iron deficiency), with and without CKD, an association between the parameters related to iron metabolism, FGF23 and markers of cardiovascular damage. 2) To evaluate in vivo, in a murine experimental model of anemia, with and without CKD, the effects of the modulation (inhibition) of triggers of iron deficiency (hepcidin) and of the increase in FGF23 (HF1α), on markers of cardiovascular damage. 3) To compare in vivo, in an experimental model of anemia with and without CKD, the effect of different I.V. iron presentations (ferrous sulphate, ferric carboxymaltose and ferric citrate) on FGF23 levels and their cardiovascular impact. 4) To evaluate in vitro, in cardiomyocytes cultures, in the presence of iron deficiency, the direct effect of FGF23 on the induction of cardiac damage. 5) To evaluate in vitro, in osteoblasts cultures, the direct effect of ferrous sulphate, ferric carboxymaltose, ferric citrate and hepcidin. Methodology. The levels of intact and C-terminal FGF23 (FGF23i and FGF23c), the differential expression profile of plasma miRNAS and of proteomic, markers of cardiovascular disease, mineral metabolism, inflammation and oxidative stress and intracellular signalling pathways will be evaluated.

Conditions

Fibroblast Growth Factor 23; Anemia; CKD

Keywords

FGF23; anemia; CKD; iron deficiency; cardiovascular risk; miRNAS; inflammation

Outcome Measures

Primary Outcomes (1)

• FGF23 on the induction of cardiovascular damage in anemia with and without CKD

  Association between iron metabolism, FGF23 and markers of cardiovascular damage in anemia with and without CKD.

  3 months

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Reina Sofia Hospital´s outpatients from Nephrology, Hematology an Internal Medicine services

You may qualify if:

• Hemoglobin \< 11g/dl
• Serum ferritin \< 100 ng/ml or transferrin saturation index \< 20%

You may not qualify if:

• Weight \< 50 Kg or BMI \< 17
• Proliferative hematologic disease. Hemochromatosis
• Systemic inflammatory illness
• Human immunodeficiency virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV) infection
• Iron active treatment
• Anticoagulant treatment with coumarins
• Chronic liver disease
• Immunosuppressive therapy
• Scheduled major surgery during study period
• Pregnancy or lactation
• Drugs addiction
• Participation in others clinical trials.

Sponsors & Collaborators

• Maimónides Biomedical Research Institute of Córdoba: lead
• Fondo de Investigacion Sanitaria: collaborator

Study Sites (1)

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

RECRUITING

Related Publications (5)

• Martin-Malo A, Borchard G, Fluhmann B, Mori C, Silverberg D, Jankowska EA. Differences between intravenous iron products: focus on treatment of iron deficiency in chronic heart failure patients. ESC Heart Fail. 2019 Apr;6(2):241-253. doi: 10.1002/ehf2.12400. Epub 2019 Jan 29.

  PMID: 30694615 RESULT

• Rodelo-Haad C, Santamaria R, Munoz-Castaneda JR, Pendon-Ruiz de Mier MV, Martin-Malo A, Rodriguez M. FGF23, Biomarker or Target? Toxins (Basel). 2019 Mar 22;11(3):175. doi: 10.3390/toxins11030175.

  PMID: 30909513 RESULT

• Rodriguez-Ortiz ME, Alcala-Diaz JF, Canalejo A, Torres-Pena JD, Gomez-Delgado F, Munoz-Castaneda JR, Delgado-Lista J, Rodriguez M, Lopez-Miranda J, Almaden Y. Fibroblast growth factor 23 predicts carotid atherosclerosis in individuals without kidney disease. The CORDIOPREV study. Eur J Intern Med. 2020 Apr;74:79-85. doi: 10.1016/j.ejim.2019.12.008. Epub 2019 Dec 31.

  PMID: 31899053 RESULT

• Rodriguez-Ortiz ME, Gomez-Delgado F, Arenas de Larriva AP, Canalejo A, Gomez-Luna P, Herencia C, Lopez-Moreno J, Rodriguez M, Lopez-Miranda J, Almaden Y. Serum Magnesium is associated with Carotid Atherosclerosis in patients with high cardiovascular risk (CORDIOPREV Study). Sci Rep. 2019 May 29;9(1):8013. doi: 10.1038/s41598-019-44322-z.

  PMID: 31142774 RESULT

• Rodriguez-Ortiz ME, Diaz-Tocados JM, Munoz-Castaneda JR, Herencia C, Pineda C, Martinez-Moreno JM, Montes de Oca A, Lopez-Baltanas R, Alcala-Diaz J, Ortiz A, Aguilera-Tejero E, Felsenfeld A, Rodriguez M, Almaden Y. Inflammation both increases and causes resistance to FGF23 in normal and uremic rats. Clin Sci (Lond). 2020 Jan 17;134(1):15-32. doi: 10.1042/CS20190779.

  PMID: 31860056 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples Urine samples

MeSH Terms

Conditions

Anemia; Iron Deficiencies; Inflammation

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Juan Muñoz Castañeda, MD

  Maimónides Biomedical Research Institute of Córdoba

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Casimiro Valle Domínguez, MD

CONTACT

34 957010000; casimiro.valle.sspa@juntadeandalucia.es

Alejandro Martín-Malo, PhD, MD

CONTACT

34 957010000; amartinma@senefro.org

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2021
• First Posted: May 2, 2022
• Study Start: October 18, 2021
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)