Iron is the basic raw material for the synthesis of hemoglobin. Epidemiological and clinical trial results confirm that a certain degree of iron deficiency is often present in patients with CKD anemia. Iron deficiency is the main cause of poor response to erythropoiesis-stimulating agents (ESAs) therapy.
Effective iron supplementation can improve anemia and reduce the dose of ESAs, and some patients can improve anemia without ESAs. patients with CKD anemia should be routinely evaluated for iron status to find the cause of iron deficiency, and iron supplementation should be administered accordingly to the patient’s iron reserve status.
In hemodialysis patients, there are factors such as blood loss from dialysis line and frequent blood collection that lead to iron loss, and certain drugs and inflammatory status can affect iron absorption, all of which should be evaluated and corrected.
1. Evaluation of iron status and frequency of monitoring
Serum ferritin (sF) and transferrin saturation (TSAT) are routinely used as the evaluation index of iron status. If available, reticulocyte hemoglobin content can be used as the evaluation index of iron status in hemodialysis patients, with a target value of >29 pg/cell.
Patients with CKD treated with stable ESAs, non-dialysis patients with CKD stages 3-5 not treated with ESAs, and maintenance hemodialysis patients not treated with ESAs should have their iron status monitored once every 3 months.
The frequency of iron status monitoring should be increased when the following conditions occur to decide whether to start, continue or stop iron therapy: when ESAs therapy is started; when the dose of ESAs is adjusted; when bleeding is present; when the efficacy is monitored after intravenous iron therapy; when there are other conditions that lead to changes in iron status, such as uncontrolled co-inflammatory infections.
2. Indications for iron therapy
In adult patients with CKD anemia not treated with iron or ESAs and with a transferrin saturation (TSAT) of ≤ 30% and ferritin ≤ 500 μg/L, it is recommended to try intravenous iron therapy. In non-dialysis patients with CKD, oral iron therapy may be attempted for 1 to 3 months, and if ineffective can be switched to intravenous iron therapy.
In adult patients with CKD anemia who have been treated with ESAs but not iron therapy, it is recommended to try intravenous iron therapy if they need to improve their hemoglobin levels or wish to reduce the dose of ESAs and have a transferrin saturation (TSAT) ≤ 30% and ferritin ≤ 500 μg/L. In non-dialysis patients with CKD, oral iron therapy may be attempted for a period of 1 to 3 months, and if ineffective may be switched to intravenous iron therapy.
μg/L In principle, intravenous iron therapy is not routinely applied. If acute phase inflammation is excluded and high-dose ESAs still do not improve anemia, iron therapy can be tried.
3.Iron usage and dose
Non-dialysis patients and peritoneal dialysis patients can try iron supplementation by oral route first, or apply intravenous iron therapy directly according to the iron deficiency status.
Hemodialysis patients should give priority to intravenous iron supplementation.
Oral iron supplementation: the dose is 200 mg/d, and the iron status is evaluated again after 1 to 3 months. If the iron status and hemoglobin do not reach the target value (under the treatment condition of 100-150 IU/kg body mass of ESAs per week), or if the oral iron is not tolerated, it is recommended to switch to intravenous iron supplementation.
Intravenous iron supplementation: ①Patients on hemodialysis should be routinely treated with intravenous iron supplementation. 1 course of treatment is often at a dose of 1000 mg, and a course of treatment can be repeated if serum ferritin is still ≤500 μg/L and TSAT <30% after completion of a course of treatment. ②Iron maintenance therapy by intravenous route: When iron status is achieved, the dose and time interval of applied iron should be adjusted according to the patient's response to iron, iron status, hemoglobin level, ESAs dosage, ESAs reaction and recent complications, and 100 mg is recommended once every 1 to 2 weeks.
If a patient has a TSAT ≥ 50% and/or serum ferritin ≥ 800 μg/L, intravenous iron supplementation should be discontinued for 3 months, followed by repeated testing of iron indicators to determine whether intravenous iron supplementation is resumed. When TSAT and serum ferritin fall to ≤50% and ≤800μg/L, respectively, intravenous iron supplementation can be considered to resume, but the weekly dose should be reduced by 1/3 to 1/2.
4.Iron treatment precautions
When the initial dose of intravenous iron therapy is given, the patient should be monitored within 60 min of infusion, with resuscitation equipment and medications, and with professionally trained medical personnel to assess serious adverse reactions.
Intravenous iron therapy is contraindicated in the presence of active systemic infection.