1.-Iron is absorbed from jejunum carried on transferrin and stored in paranchymatous organs as ferritin and haemosidrin. 2.-Serum ferritin is an indicator of iron overload which commonly used in clinical practice. 3.Ferritin concentration equal or more than 1000 ng/ml is indication of iron chelation and use of desferoxamine therapy.

 In our unit; in hemodialysed children monthly assessment of iron indices will be done for proper action of erythropiotein  The result was 9 patients suffer from high serum iron with range from ( µg/ml), high serum ferritin ranged from ( ng/ml) and transferrin saturation ranged from (55%-75%) (Group I).  These results push us to do this study and to try to find out: -Possible underlying aetiology. -Proper therapy. -Avoidance of its complications. Another 10 patients (group II) with normal or low ferritin level.

1- Possible underlying aetiology: A- Serum ferritin is an acute phase reactants which may be increased in chronic infections or inflammation so chronic hepatitis C infection may play a role in increased level of ferritin. HCV Serum ferritin Iron overload ChronicityLiver cirrhosis

B- Aluminum intoxication is a common problem in hemodialysed children Iron overload Ineffective erythropoiesis Aluminum Transferrin Free iron Abnormal RBCs Hemolysis Anaemia

D- Hyperparathyrodism Ostitis fibrosa cystica Myelofibrois Refractory anaemia Iron overload Repeated bl. Transfusion

E- Uremic toxicity and shortened RBCs life span. F- Repeated blood transfusion cause iron overload and hepatitis C infection G- Exogenous iron intake especially paranteral route

C- Anemia of chronic diseases (ACD): Characterized by reduced serum iron and iron binding capacity and raised serum ferritin. Iron accumulation Pathogenesis : 1- Mild decrease in red cell life span. 2- Disturbance of erythropoiesis. 3- Inflam. cytokines mainly TNF α. 4- Relative lack of erythropoietin. 6- Disturbance in iron metabolism:

Hepcidin is expressed predominantly in the liver, but lower expression was also detected in the kidney, heart, skeletal muscles and brain. It is consistent with hormonal-type regulation. Moreover, it has been suggested that the kidneys are not only involved in the synthesis of hepcidin, but may also be involved in the elimination of this peptide. hepcidin was produced as an intrinsic peptide in the epithelial cells of the tubule and collecting duct in mammalian kidney and may also be released luminally into the urine.

Hepcidin plays a role as a negative regulator of intestinal iron absorption and iron release from macrophages. Evidence from transgenic mouse models indicates that hepcidin is the predominant negative regulator of: iron absorption in the small intestine, iron transport across the placenta, and iron release from the macrophages. Hepcidin controls intestinal iron absorption by regulating ferroportin expression on the basolateral membrane of enterocytes.

The net effect of hepcidin is the diminished absorption of dietary iron, sequestration of iron in macrophages and sequestration of iron in hepatic stores.

*Institution of an iron-free diet, *production of the anemic state, *hypoxia are associated with decreased hepcidin production, while increased hepcidin production is noted in *inflammation

 During the inflammatory process the following cytokines are primarily produced by macrophages and monocytes: interleukin (IL)-6, IL-1 , tumor necrosis factor-  (TNF-  ), interferon- , and transforming growth factor (TGF)- .  They stimulate acute-phase protein production, with IL-6 being the major inducer of the majority of acute-phase reactants.  This family of cytokines also suppresses hepatic albumin synthesis.  IL-6 is apparently a key inducer of hepcidin synthesis during inflammation

serum C-reactive protein (CRP) or IL-6, which are inversely correlated with creatinine clearance. Patients with a chronic kidney disease have a chronic inflammatory state.This is due to many underlying factors, including : enhanced incidence of infections, the uremia, elevated levels of proinflammatory cytokines frequent presence of widespread arteriosclerosis,

There are additional factors on hemodialyses, which may contribute to this process (impure dialysate, bioincompatible dialysis membranes, intercurrent infections

Nineteen patients were undergo :  Iron indices (serum iron, TIBC, serum ferritin, transferrin saturation).  Serum aluminum level.  Serum TNF α  C-reactive protein.  Parathormone level.  Serum albumin level.  Hepatitis markers.  Number of blood transfusion.  Number of serious bacterial infection.  MRI liver.

 Patients with serum ferritin > 1000 ng/ml, 9 patients were subjected to desferal therapy. At the dose of 10 mg/kg /BW by I.V infusion 4-6 hours just before session 3 times weekly  Re-evaluation of iron indices monthly  We didn’t give more than 6 doses monthly to minimize the hazards of chronic desferrox- amine administration. Why?

 The goal of iron chelation therapy is to prevent iron-mediated injury to cells.  Free iron  injurious compounds as hydroxyl radical.  Iron overload and infection:  Removal of iron from potential pathogens is a host defense strategy.  Iron overload in these patients adds to an already compromised defensive network.

RESULTS The results of this study which was done from February 2004 to March 2005 were as follow.

MRI abdomen show iron deposition in liver and spleen in T2. T1T2

MRI abdomen show excessive iron deposition in liver & spleen in T2. T1T2

CONCLUSION Iron overload is one of major problems in hemodialysed children which must be treated and followed up to minimize it’s complications. Desferroxamine 10 mg/kg/B.W is beneficial in the minimizing iron overload with no obvious complica- tions during one year study.

 Repeated assessment of iron status.  Treatment of underlying causes if possible.  Decrease frequency of blood transfusion as possible.  Attention must be given for exogenous iron administration especially by paranteral route.  Future comparative study of oral iron chelating versus desferroxamine. RECOMMENDATIONS

After this study we try to solve the problem by: 1-Regular iron chelation by desferal (desferroxamine) therapy by intravenous infusion in the dose of 10 mg/ kg/Bw 4-6 hours immediately just before session for maximum 10 doses per month. We have three patients showed desferroxamine hypersensitivity we use oral deferiprone (deferiprox or kelever) in the same dose if 10 mg/kg oral with successful reduction of serum ferritin level. With future therapy we should use oral iron chelating agents with interavenous form to chelate both hepatic and cardiac iron overload.

2-Regular aluminum chelation by desferal at the dose of 5 mg/kg/ 4-6 hrs before session once weekly -3Close follow up of parathormone and treat hyperparathyroidism by interavenous one alpha and proper control of calcium and phosphorus levels. 4-Decrease the frequency of blood transfusions as possible. 5-Proper treatment of infection. 6-Accurate calculation of interavenous iron and only when needed. 7-Efficient dialysis to improve B.M functions, B.M response to erythropiotein and RBCs life span.

8-We try to increase the dose and frequency of erytheropiotein in patients with Iron overload. 9-In patients with low serum iron and high serum ferritin we use interavenous iron followed immediately by I.V erytheropiotein by high dose 150 I.u/kg in a trial to push iron in B.M to enhance erytheropiosis (our unit trial). 10-Interavenous L carnitine was used in children with iron overload to protect heart from oxidative stress. 11-Regular interamuscular long acting vit B12 and oral vit B6, B1 and folic acid to enhance B.M functions.

12- Future Therapy:* Antioxidants to decrease the oxidative stress of iron overload. Hepcidin Antagonist as vit C. (Malyszko 2007) Anti TNFα in a trial to minimize cytokine that disturb iron metabolism.

Finally, iron overload in hemodialysed children is respond to treatment by desferal and by solving the others underlying problems. But the course is fluctuating since ferritin become high again after stoppage of desferal especially if anemia of chronic disease is the cause.