IRON STATUS
Research is still in progress and there is controversy over which tests of iron status should be used in patients receiving erythropoietin. Many such tests exist, all of which assess different parts of the iron metabolic pathway, and no one single test can be used to give a global picture of iron status. Thus, the serum ferritin gives an approximate indication of iron stores, the transferrin saturation assesses how much iron is circulating in plasma relative to the total iron-binding capacity (transferrin), and the percentage of hypochromic red cells has been advocated as the best means of assessing how much iron is being incorporated into the red cell. Iron stores are said to be normal or near-normal when serum ferritin maintained above 100 µg/L, the transferrin saturation above 20%, and the proportion of hypochromic red cells below 10%.
Iron deficiency is found in up to 40% of renal failure patients with erythropoietin therapy. There are two conditions representing inadequate iron status, namely absolute iron deficiency and functional iron deficiency. Absolute iron deficiency is present when the total body iron stores are inadequate, as judged by a low serum ferritin. Functional iron deficiency exists when there are ample or even increased iron stores, but these stores are unable to release their iron rapidly enough to satisfy the demands of the bone marrow for erythropoiesis. Both conditions will result in a suboptimal response to erythropoietin and will require aggressive iron supplementation. Renal failure patients require high iron availability to maximize use of exogenous erythropoietin and maintain satisfactory hematocrit.
Administration of oral iron is often inadequate in hemodialysis and peritoneal dialysis patients, and intravenous iron is often required. There are several IV iron preparations available, differing in molecular weights, degradation kinetics, availability profiles, and adverse effects, and various dosing regimens have been suggested. Frequent ‘‘low-dose’’ administration of 20–60 mg of iron every dialysis session has been advocated in hemodialysis patients, but this is impractical for peritoneal dialysis patients who neither have ready vascular access nor are attending hospital regularly. In this latter group, larger infusions of 300–1000 mg of IV iron can be given every month or so. If constipation is seen in CAPD patients oral iron to be avoided and most patients suffer gastrointestinal side effects with oral iron supplementation.
INTRAVENOUS IRON
Studies showed that aggressive iron supplementation for anemia in renal failure rarely produced a complete correction of anemia but raise of 1-2 g/dL of hemoglobin is seen even in iron-replete patients. After the introduction of erythropoietin, IV iron is used to enhance the response to erythropoietin. Intravenous iron should be withheld when serum ferritin >800 ng/ml.Intravenous iron should not be given when infection is present because of the theoretical risk that neutrophil function may be adversely affected. Macrocytosis developing during iron supplementation may reflect the development of folate deficiency.
Adverse effects of Intravenous iron include; hypotension, nausea, vomiting, sweating, back pain, pruritis and a sudden feeling of being unwell.
Intravenous Iron Preparations:
Three preparations of Intravenous irons are available; iron sucrose/iron III hydroxide sucrose complex (Iron Saccharate), Sodium ferric gluconate and iron dextran.
Iron Sucrose:
Widely used and efficacious with a low incidence of adverse reaction. No need for test dose before first administration.
- Dosing: 100mg at the end of hemodialysis on 10 successive dialysis sessions if serum ferritin is<200 ng/ml. Later 100mg weekly once at end of hemodialysis while serum ferritin <600 ng/ml. 200mg of iron sucrose can be given once in 1 – 3 months in peritoneal dialysis and pre-dialysis patients as an Intravenous Infusion.
- Can be given slow intravenous injection at 20 mg /min or as intravenous infusion.
- Administration Protocols: 100 – 200 mg undiluted over 5 – 10 min 20 mg/min is recommended. 100 mg undiluted over 2 min reported to be safe, 100 mg in 100 ml of normal saline over 15 min.
- Changes in transferrin saturation and ferritin levels can be measured 48 hrs after intravenous administration.
Sodium Ferric Gluconate ( Ferrlecit)
- Non-dialysable and no need for test dose before initial administration.
- Common mild reactions
- Usually given as 60 – 125 mg of Intravenous infusion undiluted over 5 – 10 min (12.5 mg/min) during consecutive dialysis session until 1 g is administered. Later 125 mg weekly while serum ferritin <600 ng/ml.
- Larger doses can be given in peritoneal and pre-dialysis patients; 300mg once in 3 months over 90 min to prevent frequent hospitalization or 125 mg in 100 ml normal saline over 60 min.
Iron dextran
- Risk of anaphylactic reactions is more
- Can lead to a generation of antidextran antibodies
- A test dose of 20 mg diluted in 50 ml saline over 30 min, because of the risk of anaphylaxis.
- Other adverse effects include itching, dyspnoea, and wheezing, arthralgia, myalgia, fever, headache.
- Usually 20 – 100 mg for 10 – 20 hemodialysis sessions done to initially treat iron deficiency, later 50- 100 mg intermittently usually weekly, fortnightly or monthly to maintain iron stores. Alternatively, 250 mg over half an hour monthly given at the end of dialysis bt slow injection or infusion.
- In CAPD or predialysis patients, 500 mg can be diluted into 250 ml saline and given over 30 – 60 min.
- Less used because of wide adverse reactions.
IRON AND FOLATE DEFICIENCY
Iron deficiency is commonly seen in most of Hemodialysis patients due to the major loss of iron (about 4-5mg per treatment) partly due to blood loss in dialysis extracorporeal circuit, occult gastrointestinal bleeding and repeated phlebotomy. Excessive loss of hematinic substances is seen in dialysis patients especially Folate as it is readily removed by hemodialysis. Dietary insufficiency may also cause these deficiencies as most of the dialysis patients suffer from poor appetite.
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