Science Journal of Medicine and Clinical Trials
March 2015,Volume 2015, ISSN: 2566-7487
© Author(s) 2015. This work is distributed under the Creative Commons Attribution 3.0 License.
Assessment of Potential Role of Fibroblast Growth Factor 23 and Klotho Gene Polymorphism in Cardiovascular Calcification Associated with Chronic and End Stage Renal Diseases
Iman A.Sharaf 1,2, Madiha H. Helmy2, Eman S D. Khalil3 and Mofeed A. Badah2
1Biochemistry Department, Faculty of Science for Girls,
King Abdulaziz University, P.O Box 51459, Jeddah 21453, Saudi Arabia
1,2 Biochemistry Department , Medical Research Institute, Alexandria University, Egypt
3Internal Medicine Department, Medical Research Institute, Alexandria University, Egypt
Accepted 25 January, 2015; Available Online 21 March,2015
Background:The high cardiovascular mortality in patients with chronic kidney disease (CKD) is closely associated with vascular
calcification (VC). Defects in endogenous anti-calcification factors such as fibroblast growth factor 23 (FGF23), and Klotho may play
an important role in these complications of CKD.
FGF23 inhibits secretion of parathyroid hormone (PTH). This effect is dependent on the presence of klotho, which is highly
expressed in the kidney and the parathyroid glands and acts as a co-receptor for FGF23 by markedly increasing the affinity of FGF23
for ubiquitous fibroblast growth factor receptors FGFRDefects in either FGF23 or Klotho cause a combination of metabolic
disturbances, including hyperphosphatemia, hypercalcemia, and hypervitaminosis.
Aim of the work: The aim of this study was to determine the possible effects of FGF23 and klotho gene polymorphisms (KL-VS and
C1818T) on the cardiovascular calcification in relation to mineral metabolism in chronic kidney diseases (CKD) and end stage renal
Subject and Methods: The present study was conducted on sixty subjects. Forty patients, recruited from the outpatient clinic of the
Nephrology Department Medical Research Institute, Alexandria University, were classified in to two groups Group 1: Included
twenty Chronic Kidney Disease patients' stages 3-5. Their mean age was 48.3 ± 12.5.Group2: Included twenty hemodialysis patients
under maintenance hemodialysis for one year (3 times/week and 4hours/session) on polysulphon membrane. Their mean age was
49.1 ± 12.5. Control subjects: Included twenty healthy volunteers of comparable age and sex to the patients groups. Written
consents will be obtained from all participants before being involved in the study.
The following was done to all the enrolled subjects:
* To all participants general health parameters assessed included screening history, physical examination, blood tests (FGF23, sKlotho, Ca, Pi, Creatinine, Urea, Uric acid, Total cholesterol, Triglyceride, Albumin and Total protein).
* Ultrasound examination of common carotid artery (CCA) to determine Carotide Intima media thickness (CIMT).
* Molecular study [genotyping of KL-VS and C1818T] polymorphisms of Klotho by polymerase chain reaction /restriction fragment length polymorphism (PCR/RFLP)].
Results: In the present study, serum levels of FGF23 showed significant increase in the mean values (p≤0.05) in the CKD and ESRD groups as compared to normal control group 1. There was an inverse relationship between FGF23 and eGFR of dialysis patients when compared to healthy controls. Levels of Klotho showed a decrease in the mean values in CKD and dialysis groups as compared to normal control group (p≤0.05). In this study, patient groups with lower levels of serum Klotho exhibited significantly lower (p≤0.05) eGFR levels. The present study revealed significant increases in the parathyroid hormone levels, the phosphorus levels , triglyceride levels and cholesterol levels in the stud groups as compared to the normal control group (p≤0.05). This study showed a significant increase in CIMT in CKD and dialysis compared with the values reported for normal populations (p≤0.05). In the present study no correlation was found between CIMT and serum levels of calcium, phosphorus and PTH in HD patients. Negative correlation was found between CIMT and serum levels of Klotho and eGFR in HD patients. The study also showed a significant relationship between CIMT and age in CKD. Negative correlation was found between CIMT and serum levels of FGF23 and calcium in CKD patients. In the molecular study of Klotho gene polymorphism, we did not detect kl-vs and C1818T polymorphism in patients who underwent CKD and dialysis which requires further investigations to elucidate the revolutionary origin of this variant or any other mechanism involved Conclusion:
* High serum FGF-23 concentrations predict more rapid disease progression in CKD patients who were not on dialysis and increased mortality in patients on maintenance hemodialysis. FGF-23 may therefore prove to be an important therapeutic target for the management of CKD and cardiovascular disease.
* Reduced Klotho protein levels with progressive renal failure may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations.
* Although we were unable to specifically identify the causal variant in the klotho gene, this work provides important information in understanding how renal disease progresses to end-stage kidney failure.
Keyword: CRONIC KIDNEY DISEASE,FIBROBLST GROWTH FACTOR-23, KLOTHO, Carotide Intima media thickness, parathyroid hormone, hemodialysis patients, Klotho gene kl-vs and C1818T polymorphism