الفهرس 
ERYTHROPOIESISOnly 14 pages are availabe for public view
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Abstract
A
nemia is a major complication of chronic kidney disease (CKD). Although pathogenesis of anemia in CKD is multifactorial involving inadequate erythropoietin production and iron- restricted erythropoiesis, a large number of CKD patients suffer from insufficient iron stores (Rohrig et al., 2013).
Treatment of CKD-associated anemia has been dramatically advanced by the introduction of recombinant human erythropoietin (EPO). However, CKD-associated anemia can be resistant to EPO treatment. In addition to EPO deficiency, inflammatory effects of the primary disease, inflammatory effects of its complications and of its treatments, and iron-restricted erythropoiesis could be involved in this pathogenesis. To achieve the optimal effect of EPO treatment, adequate iron management in patients with CKD-associated anemia is essential. Although serum ferritin and transferrin saturation (TSAT) are commonly used as biomarkers for iron status in CKD patients, these markers are not sensitive enough to distinguish functional iron deficiency from iron overload (Uehata et al., 2011).
Therefore, Hepcidin, a 25-amino acid peptide primarily produced in the liver, is thought to be the central regulator of body iron metabolism. Hepcidin controls the plasma iron concentration by inhibiting iron export by ferroportin from enterocytes and macrophages. Therefore, increased hepcidin production leads to a decrease in plasma iron concentrations and to iron-restricted erythropoiesis. Hepcidin expression is induced by iron loading and by inflammation and is suppressed by erythropoietic activity. Studies of humans with chronic infections and severe inflammatory disease have shown markedly increased levels of hepcidin, strongly suggesting that elevated hepcidin levels play a key role in the anemia of inflammation and reticuloendothelial blockade. It is plausible that increased hepcidin concentrations may cause iron-restricted erythropoiesis also in CKD-associated anemia (Kemna et al., 2008).
The present study investigated the cross talk between iron metabolism, inflammation and erythropoiesis in CKD. The aim of the present study was (1) Detection of Hepcidin level in Egyptian patients with CKD. (2) Comparison of Hepcidin levels in CKD and healthy subjects. (3) Correlation of Hepcidin level, iron profile and degree of anemia in CKD group and healthy group.
This study was conducted on 50 patients, who were admitted to Dar El-Shefaa Hospital, during 2014- 2015. They were previously diagnosed as CKD. Ten healthy age and sex-matched subjects served as a control group. All subjects involved in the control group were free from any other conditions that may affect serum Hepcidin level such as inflammation.
In the present study, the CKD group comprised 20 males (40%) and 30 females (60%), their age ranged from 28 to 75 years with a mean age of 55.76 ± 10.93 years. The 10 healthy control group comprised 4 males 40%) and 6 females (60%), their age ranged from 27 to 57 years with a mean age of 44.80 ± 11.20 years.
The enrolled patients were subjected to full history taking, thorough clinical examination laying stress on pallor, glossitis and stomatitis and routine laboratory investigations: CBC, iron profile, Renal function tests and measurement of serum Hepcidin using ELISA kit obtained from R&D (R&D system.
The present results showed statistically significant correlation between serum Hepcidin and age between studied groups (p = 0.024). Meanwhile, regarding gender of patients there was statistically significant correlation in Hepcidin levels between male and female patients (p =0.032)
The mean value of Hepcidin concentration was statistically highly significantly increased in CKD group (98.59 ± 22.44 µg/L), than that of the controls (34.0 ± 5.52µg/L), (p ≤0.001).
The CKD group had statistically highly significant (p≤0.001) decrease in mean values of hemoglobin (Hb), (10.16 ± 1.67g/dl ) than the control group (13.02 ± 1.422 g/dl).
Regarding the red cell indices, the present study documented a statistically non-significant correlation between serum Hepcidin and MCV and MCH between CKD and control groups. But regarding hemoglobin the study showed statistically significant negative correlation (r =-0.492 and p ≤ 0.001).
Considering the relation between serum Hepcidin and the iron profile, the present results showed no significant correlation between serum Hepcidin and serum iron and TIBC, between studied groups. Thus, the correlation of Hepcidin level, iron profile and degree of anemia in CKD could not be established, as the relation between the ferritin and Hepcidin was statistically significant but serum ferritin is more considered as an acute phase reactant and expressed as a result of chronic inflammation.
Finally, the present study clearly demonstrated that there was a statistically highly significant difference in serum Hepcidin level between the CKD group versus control group of patients. Thus, measuring serum Hepcidin (by ELISA), can be used as a potential marker in the assessment of anemia in the clinical practice. The ELISA is a sensitive, specific, quantitative and reliable technique, with relatively stable reagents. Moreover, it is quick, convenient, generally safe (no radioactive decay) and is used in a wide variety of laboratories.
Moreover, the current study demonstrated that, Hepcidin plays a role in the pathogenesis of anemia of CKD. Although Hepcidin is linked to the need for erythropoiesis and iron homeostasis in iron deficiency anemia, the significantly increased circulating concentrations of this protein in anemia of CKD suggests that hepcidin has a role.