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

Not Applicable

Suspended

• Conditions: Endothelial Dysfunction; Left Ventricular Hypertrophy; Anemia of Chronic Kidney Disease; Fibroblast Growth Factor 23
• Interventions: Diagnostic Test: detailed echocardiography; Diagnostic Test: serum fibroblast growth factor-23; Diagnostic Test: flow mediated dilatation of forearm

• Registration Number: NCT03193073
• Lead Sponsor: Omnia Mohammed Hashem

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.

Detailed Description

1. To study the effect of anemia correction and left ventricular hypertrophy in Chronic Kidney Disease patients and renal transplant patients .

2. To study the relation of fibroblast growth factor and Left ventricular hypertrophy in Chronic kidney disease and renal transplant patients.

3. To study the relation between fibroblast growth factor 23 and early endothelial dysfunction in both Chronic kidney disease and renal transplant patients.

Study Timeline

• Study First Submitted: 2017-05-26
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-20
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-25
• Last Update Posted: 2018-06-27
• Study Start: 2018-09-01
• Primary Completion: 2020-09-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

All patients:

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

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Newly renal transplanted patients .	flow mediated dilatation of forearm	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
CKD patients with different stages	serum fibroblast growth factor-23	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 .
CKD patients with different stages	detailed echocardiography	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 .
CKD patients with different stages	flow mediated dilatation of forearm	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 .
Newly renal transplanted patients .	serum fibroblast growth factor-23	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
Newly renal transplanted patients .	detailed echocardiography	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

Primary Outcome Measures

Name	Time	Method
if change of in Hemoglobin level and correction of anemia associated with change in the left ventricular outcomes	measures at time of diagnosis then after 3 months	measure the left ventricular mass index (gm/m2)
the relationship between the FGF-23 and degree of left ventricular dysfunction	measure at time of diagnosis	measure FGF-23 level in (pg/ml)
the relationship between FGF-23 level and early endothelial dysfunction	at time of diagnosis in chronic kidney disease / after 6 months in renal transplant	change in arterial diameter in mm

Trial Locations

Locations (1)

Assiut University Hospitals; 🇪🇬 Assiut, Egypt