Clinical trial NCT03193073: Anemia Correction and Fibroblast Growth Factor 23 Levels in Chronic Kidney Disease , and Renal Transplant Patient
Official title: Impact of Anemia Correction and Fibroblast Growth Factor 23 Levels in Left Ventricular Hypertrophy, and Early Endothelial Dysfunction in Chronic Kidney Disease, and Renal Transplant Patient
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Anemia of Chronic Kidney Disease
Endothelial Dysfunction
Left Ventricular Hypertrophy
Fibroblast Growth Factor 23
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-06-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: if change of in Hemoglobin level and correction of anemia associated with change in the left ventricular outcomes
timeFrame: measures at time of diagnosis then after 3 months
measure: the relationship between the FGF-23 and degree of left ventricular dysfunction
timeFrame: measure at time of diagnosis
measure: the relationship between FGF-23 level and early endothelial dysfunction
timeFrame: at time of diagnosis in chronic kidney disease / after 6 months in renal transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut University Hospitals
Study officials:
affiliation: Assiut University
name: Mohammed Ali Tohamy, professor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.