Anemia Correction and Fibroblast Growth Factor 23 Levels in Chronic Kidney Disease , and Renal Transplant Patient

NCT03193073 | Suspended

• 1 other identifier: 17200031
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The fibroblast growth factor-23-bone-kidney axis is part of newly discovered biological systems linking bone to other organ functions through a complex endocrine network that is integrated with the parathormone/vitamin D axis and which plays an equally important role in health and disease . Most of the known physiological function of fibroblast growth factor 23 to regulate mineral metabolism can be accounted for by actions of this hormone on the kidney.In a recent experimental study, fibroblast growth factor-23 was shown to cause pathological hypertrophy in rat cardiomyocytes by "calcineurin-nuclear factor of activated T cells" and treatment with fibroblast growth factor -blockers reduced left ventricular hypertrophy in experimental models of chronic renal failure.The current hypothesis is that, in healthy individuals, iron deficiency stimulates increased production of fibroblast growth factor23. At the same time, iron is thought to be the cofactor of enzymes taking part in the degradation of intact fibroblast growth factor-23 and thought to have a role in the excretion of degraded FGF-23 parts .Studies speculated that Angiotensin Converting Enzyme inhibitors may exert their anti-proteinuria effects at least in part by reducing serum fibroblast growth factor-23 levels although it is difficult from the results of this study to understand which comes first and brings about the other; decrease in proteinuria or fibroblast growth factor-23. Available evidence points to the deleterious effects of increased fibroblast growth factor-23 level in proteinuria, but the precise molecular mechanism still remains to be explored. An intricate and close association exists among parathormone, phosphorus, active vitamin D with FGF23, but the independent role of the latter on proteinuria is the least explored. Elaborately conducted studies that control effects of confounding factors adequately are needed to demonstrate the independent pathogenic role of FGF23.

Conditions

Anemia of Chronic Kidney Disease; Endothelial Dysfunction; Left Ventricular Hypertrophy; Fibroblast Growth Factor 23

Outcome Measures

Primary Outcomes (3)

• if change of in Hemoglobin level and correction of anemia associated with change in the left ventricular outcomes

  measure the left ventricular mass index (gm/m2)

  measures at time of diagnosis then after 3 months

• the relationship between the FGF-23 and degree of left ventricular dysfunction

  measure FGF-23 level in (pg/ml)

  measure at time of diagnosis

• the relationship between FGF-23 level and early endothelial dysfunction

  change in arterial diameter in mm

  at time of diagnosis in chronic kidney disease / after 6 months in renal transplant

Study Arms (2)

CKD patients with different stages

ACTIVE COMPARATOR

1. Full clinical history and through clinical examination. 2. Full blood count at time of diagnosis and 3 months after initiation of treatment with iron and erythropoietin Stimulating agents. 3. Iron study at time of diagnosis and 3 months after treatment . 4. Serum calcium , phosphorus, intact Parathrmone hormone. 5-24- urinary proteins or Albumin Creatinine ratio every month (for 3 months )then every 3 months (1 st year), then annually. 6- Lipid profile . 7-Estimated glomerular filtration rate by MDRD equation .

Diagnostic Test: detailed echocardiography; Diagnostic Test: serum fibroblast growth factor-23; Diagnostic Test: flow mediated dilatation of forearm

Newly renal transplanted patients .

ACTIVE COMPARATOR

1. Full clinical history and through clinical examination. 2. Pre transplant Serum calcium , phosphorus , I Parathrmone hormone , serial measures every / 3 months for 2 years. 3. Pre-transplant full blood count serial measures every / 3 months for 2 years. 4. Pre transplant serum Iron study and annually for 2 years. 5. 24- urinary proteins or albumin-creatinine ratio every month (for 3 months )then every 3 months (1 st year), then annually. 6. Post-transplant serum FGF-23 (as independent risk factor) at 6months. 7. Different immunosuppressive protocols. 8. Pre-transplant panel reactive antibody,donor-specific antibody

Diagnostic Test: detailed echocardiography; Diagnostic Test: serum fibroblast growth factor-23; Diagnostic Test: flow mediated dilatation of forearm

Interventions

detailed echocardiography DIAGNOSTIC_TEST

Detailed Echocardiography including ejection fraction, interventricular septum thickness, posterior wall thickness, left ventricular end -diastolic and end- systolic diameter and left ventricular mass index will be correlated with body surface area for both groups serum FGF-23

CKD patients with different stages; Newly renal transplanted patients .

serum fibroblast growth factor-23 DIAGNOSTIC_TEST

serum levels of FGF-23

CKD patients with different stages; Newly renal transplanted patients .

flow mediated dilatation of forearm DIAGNOSTIC_TEST

superficial sonar assess the diameter of brachial vessel on exposure to stress

CKD patients with different stages; Newly renal transplanted patients .

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• All patients:
• Above 18 years old
• Diagnosed as CKD, and renal transplanted patients at Assiut University Hospital in the period 2017-2020 .

You may not qualify if:

• Severely hypocalcaemic patients \< 7mg/dl.
• Severely hyperphosphatemic patients \>7 mg/dl .
• Uncontrolled hypertensive patients ( more than 3 antihypertensive drugs).
• Uncontrolled diabetic patients HBA1C \>8 .
• Blood transfusion dependent

Sponsors & Collaborators

• Omnia Mohammed Hashem: lead

Study Sites (1)

Assiut University Hospitals

Asyut, Egypt

Location

Related Publications (5)

• Grabner A, Amaral AP, Schramm K, Singh S, Sloan A, Yanucil C, Li J, Shehadeh LA, Hare JM, David V, Martin A, Fornoni A, Di Marco GS, Kentrup D, Reuter S, Mayer AB, Pavenstadt H, Stypmann J, Kuhn C, Hille S, Frey N, Leifheit-Nestler M, Richter B, Haffner D, Abraham R, Bange J, Sperl B, Ullrich A, Brand M, Wolf M, Faul C. Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab. 2015 Dec 1;22(6):1020-32. doi: 10.1016/j.cmet.2015.09.002. Epub 2015 Oct 1.

  PMID: 26437603 RESULT

• Torun D, Yildiz I, Micozkadioglu H, Nursal GN, Yigit F, Ozelsancak R. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism. Saudi J Kidney Dis Transpl. 2016 Jan;27(1):15-22. doi: 10.4103/1319-2442.174053.

  PMID: 26787561 RESULT

• Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013 Aug;28(8):1793-803. doi: 10.1002/jbmr.1923.

  PMID: 23505057 RESULT

• Eser B, Yayar O, Buyukbakkal M, Erdogan B, Ercan Z, Merhametsiz O, Haspulat A, Oguz EG, Dogan I, Canbakan B, Ayli MD. Fibroblast growth factor is associated to left ventricular mass index, anemia and low values of transferrin saturation. Nefrologia. 2015;35(5):465-72. doi: 10.1016/j.nefro.2015.06.025. Epub 2015 Sep 26. English, Spanish.

  PMID: 26394828 RESULT

• Io H, Aizawa M, Funabiki K, Horikoshi S, Tomino Y. Impact of anaemia treatment for left ventricular remodelling prior to initiation of dialysis in chronic kidney disease patients: Efficacy and stability of long acting erythropoietin stimulating agents. Nephrology (Carlton). 2015 Dec;20 Suppl 4:7-13. doi: 10.1111/nep.12640.

  PMID: 26439537 RESULT

MeSH Terms

Conditions

Hypertrophy, Left Ventricular

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Mohammed Ali Tohamy, professor

  Assiut University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant lecturer at Assiuy university- faculty of medicine-internal medicine department

Model Details: two groups of patients (group A: CKD and group B newly transplanted patients) are assigned for detailed echocardiography , serum FGF-23, flow mediated dilatation of the forearm before anaemia correction in group A and renal transplant in group B . Also assesment of FGF-23 in different stages of group A, assessment of FGF-23 before and after renal transplant

Study Record Dates

• First Submitted: May 26, 2017
• First Posted: June 20, 2017
• Study Start: September 1, 2018
• Primary Completion: September 1, 2020
• Study Completion: December 1, 2020
• Last Updated: June 27, 2018

Record last verified: 2018-06

Locations

EG (1)