Author:Amr Raafat

Amr Raafat


Program of Masters & PhD in Medicine
Faculty of Engineering
Al-Azhar University



•••FGF-21 level and its relationship to cardiac dysfunction in chronic kidney diseases patients

Abstract Fibroblast growth factor 21 (FGF-21) was first cloned and identified from mouse embryos by homology-based PCR in 2000(Nishimura et al., 2000). Human FGF-21 is a polypeptide of 181 amino acids with 75% identity to mouse FGF-21. It is secreted predominantly by the liver (Nishimura et al., 2000), but also by other tissues involved in glucose and lipid metabolism such as the adipose tissue, pancreas and skeletal muscle (FonTacer et al., 2010). Studies in rodents have suggested FGF-21 to be a key physiological regulator of fasting response (Inagaki et al., 2007). Renal excretion is a major route for FGF-21 elimination. Serum FGF-21 levels have been shown to be increased in patients with impaired renal function. Circulating FGF-21 is increased in both acute and chronic kidney diseases. (Stein et al., 2009). Serum FGF-21 concentration was associated with residual renal function and insulin resistance in end-stage CKD patients with long-term hemodialysis (Han et al., 2010). These results suggested that FGF-21 may be related to renal excretion functions in humans. Plasma FGF-21 concentration has been shown to be increased with the development of early- to end-stage CKD following the loss of renal functions in CKD patients. These results suggest that circulating FGF-21 concentration is associated with the CKD progression (Lin et al., 2011). Patients with chronic kidney disease are at profoundly higher risk for cardiovascular (CV) morbidity and mortality. The nature of CV disease in patients with renal failure differs from that of the general population. Whereas the most common manifestations of CV disease in the general population include coronary atherosclerotic disease, patients with renal failure are far more likely to suffer from chronic heart failure and sudden cardiac death (Herzog et al., 2011).Sudden cardiac death is the leading cause of death in ESRD patients, and accounts for approximately 25% of all deaths in this population. In addition, the clinical presentation of CV disease is also different amongst those with renal disease when compared to the general population (Green et al., 2011). The current study aims to assess FGF-21level and its relationship to cardiac dysfunction in the different stages of chronic kidney disease patients. This work conducted on 100 subjects divided into 5 groups according to eGFR, each group included 20 patients where group I included 20 apparently healthy control subjects with matched age, sex and BMI, group II included 20 patients with CKD stage II, group III included 20 patients with CKD stage III, group IV included 20 patients with CKD stage IV, group V included 20 patients with ESRD on regular hemodialysis three times per week. Inclusion criteria included: Sixty CKD patients with sustained reduction(≥3 months) in estimated glomerular filtration rate (eGFR) ≤90 ml /min/1.73 m2 based on the simplified Modification of Diet in Renal Disease formula, in addition to twenty patients on regular hemodialysis three times per week. Exclusion criteria included: overweight and obesity, uncontrolled hypertension, uncontrolled diabetes, cardiac valve diseases, ischemic heart diseases and liver cirrhosis. CKD patients included in this study were recruited from nephrology outpatient clinic at AL-Housein University hospital while hemodialysis patients included in this study were recruited from hemodialysis unit at AL-Housein University hospital. All the patients were subjected to full history & detailed clinical examination at the start of the study. Levels of serum FGF-21 and serum fasting insulin were measured by ELISA technique while serum iPTH was measured by an immunoradiometric assay. Insulin resistance according to HOMA-IR = ([fasting insulin (iU/ml) x fasting glucose (gm/dl)]/405). All blood tests were done at Al-Housein University hospital main lab Serum FGF-21 level increased with the development of early to end- stage CKD patients. FGF-21 concentration is closely related to the change of renal function in CKD patients. LVMI increased with the progression of renal function also, there was no significant difference between mean LVMI in diabetics, hypertensive and other CKD patients with other comorbidities (P- value: 0.914) The present study showed that FGF-21 level was significantly correlated with LVMI(r: 0.558, P-value <0.001). After adjustment for age, sex, BMI, DM and hypertension, serum FGF-21 level still significantly correlated with LVMI but after adjustment for calcium, phosphorus, iPTH and adverse lipid profiles, serum FGF-21didn’t correlate with LVMI. These results show that neither hypertension nor DM affect FGF-21 level or LVMI and effect of FGF-21 level on LVMI is enhanced by other cofounders as calcium, phosphorus, PTH and lipids. Ejection fraction (EF) was mildly declined with the progression of CKD (P-value = 0.04). Serum FGF-21 was not significantly correlated with EF or FS (sig. = 0.064, 0.095 respectively). Diastolic functions deteriorated with the progression of CKD and serum FGF-21 level was significantly correlated with left ventricular diastolic dysfunction.


TITLE - FGF-21 level and its relationship to cardiac dysfunction in chronic kidney diseases patients
AUTHOR - Amr Raafat
••••••IJSER Edition - November 2019

UNIVERSITY - Al-Azhar University
Tarek Zakaria ElBaz
Ahmed Alaa El-din Ahmed
Safwat Farrag Ahmed