Book
Anemia in Chronic Kidney Disease (CKD)
- Executive Summary
CHAPTER 1. DIAGNOSTIC EVALUATION OF ANEMIA IN CKD
▪️ 1.1: Hemoglobin (Hb) levels should be routinely measured to screen for anemia on initial evaluation for all CKD patients (regardless age and stage of CKD). (Good practice statement)
o at least annually in patients with CKD 3 and
o at least twice a year in patients with CKD 4
o Every three months in patients with (CKD- ND) and (CKD- PD) on peritoneal dialysis
o At least monthly in patients with (CKD-HD) on hemodialysis
▪️ 1.2: In initial evaluation for anemia in people with CKD, test for anemia with: complete blood count (CBC),and if available serum ferritin, transferrin saturation (TSAT) (Good practice statement
▪️ 1.3: Patients with CKD and anemia, in whom the initial test does not reveal the cause, consider this expanded panel to identify potential underlying causes as:
o Blood smear
o C Reactive Protein (CRP)
o Test for hemolysis, (lactate dehydrogenase, haptoglobin)
o Serum vitamin B12 and folic acid levels
o Thyroid stimulating hormone (TSH)
o liver function tests, (ALT, AST)
o Serum protein electrophoresis (SPEP) with immunofixation, serum free light chains urinary Bence-Jones protein
o Occult blood in stool. (Good practice statement)
▪️ 1.4: CKD should be considered as a possible cause of anemia when the glomerular filtration rate (GFR) is <60 ml/min/1.73m2. It is more likely to be the cause if the (GFR) is< 30ml/min/1.73m2 (<45ml/min/1.73m2 in patients with diabetes) and no other cause as blood loss, folic acid or vitamin B12 deficiency, is identified. (Conditional recommendation)
▪️ 1.5: Consider referral of patients with CKD and anemia, when serum ferritin <45 µg/l, to gastroenterologists/urologists /gynecologists to identify the cause of blood loss. (Good practice statement)
CHAPTER 2. USE OF IRON TO TREAT IRON DEFICIENCY ANEMIA IN CKD
▪️ 2.1: We suggest initiation of iron therapy in patients with (CKD -HD) if serum ferritin ≤500 ng/ml (≤500 µg/l) and TSAT <30%. (Conditional recommendation)
▪️ 2.2: In people with anemia and CKD not receiving dialysis (ND)or treated with peritoneal dialysis (CKD- PD), we suggest initiating iron if:
o Ferritin <100 ng/ml (<100 µg/l) and transferrin saturation (TSAT) <40%, or
o Ferritin ≥100 ng/ml (≥100 µg/l) and <300 ng/ml (<300 µg/l), and TSAT <25%. (Conditional recommendation)
▪️ 2.3: In people with (CKD-HD) in whom iron therapy is being initiated, administer intravenous iron using a proactive approach to maintain stable iron status. (Good practice statement)
▪️ 2.4: In people with anemia and (CKD-HD) in whom iron therapy is being initiated, we suggest using intravenous iron rather than oral iron. (Conditional recommendation)
▪️ 2.5: In people with CKD treated with iron, it is reasonable to withhold iron if ferritin ≥700 ng/ml (≥700 µg/l) or TSAT ≥40%. (Good practice statement)
▪️ 2.6: For CKD patients not requiring hemodialysis, the choice between oral vs. parenteral iron depends on the severity of iron deficiency, the previous response and side effects, the availability of venous access and person’ preferences. (Good practice statement)
▪️ 2.7: In CKD patients not on dialysis switch from oral to intravenous iron if there is an insufficient effect of an optimal oral regimen after 1 to 3 months. (Good practice statement)
▪️ 2.8: In people with CKD treated with iron, it is reasonable to test hemoglobin, ferritin, and TSAT every 3 months for those not receiving dialysis or (CKD- PD) and every month for those with (CKD -HD). (Good practice statement)
▪️ 2.9: consider treatment with oral or intravenous iron in patients with CKD and profound iron deficiency (ferritin <30 µg/l and TSAT<20%) but with no anemia. (Good practice statement).
▪️ 2.10: In patients with CKD treated with IV iron resuscitative medication and trained personnel to evaluate and resuscitate anaphylaxis should be present at each administration of intravenous iron. (Conditional recommendation)
chapter 3. use of ESAs and other agents to treat anemia in CKD
3.1: Treatment initiation
▪️ 3.1.1: In people with anemia and CKD (whether treated with dialysis or not), the decision to use erythropoietin- stimulating agents (ESAs) or hypoxia- inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) to raise the hemoglobin (Hb) should consider each individual’s symptoms, potential for harm from blood cell transfusions, and potential risk of adverse events (e.g. stroke, cardiovascular event, cancer) (Good practice statement)
▪️ 3.1.2: In people with anemia and CKD in whom correctable causes of anemia have been addressed, we suggest using an ESA rather than a HIF-PHI as first-line for treatment of anemia. (Good Practice Statement)
▪️ 3.1.3: For adult CKD 5HD or PD patients, we suggest initiation of ESA therapy when the Hb is less than 9.0g/dl. (Conditional recommendation)
▪️ 3.1.4: In people with CKD not receiving dialysis, selection of Hb concentration at which ESA therapy is initiated should consider the presence of symptoms attributable to anemia, the potential benefits of higher Hb concentration, and the potential harms of RBC transfusion or receiving ESA therapy. (Conditional recommendation)
▪️ 3.1.5: In adult patients with anemia of CKD you should not routinely correct Hb to normal levels 13g/dl with ESAs therapy. (strong recommendation)
3.2: ESA maintenance therapy
▪️ 3.2.1: We recommend a hemoglobulin target between 10-11.5g/dl when treating adult CKD patients with ESAs. (Strong recommendation)
▪️ 3.2.2. In all adult patients, we recommend against using ESAs to intentionally increase the Hb above 13g/dl. (Strong recommendation)
▪️ 3.2.3: ESA doses are prefrabially decreased rather than withheld when a downward adjustment is needed. (Conditional recommendation)
3.3: ESA dosing, frequency, route of administration, and monitoring
▪️ 3.3.1: In adults with anemia and (CKD- HD) the decision of the choice of ESA is based on local availability of ESAs, the target Hb response achieved, route of administration, and cost. (Good practice statement)
▪️ 3.3.2: Hb concentration should be monitored every 2–4 weeks in the correction phase and every 1–3 months for stable patients in the maintenance phase, for (CKD -HD) measure Hb concentration every month. (Conditional recommendation)
▪️ 3.3.3: In people with anemia and CKD treated with ESA, avoid adjusting the dose of ESA more frequently than once every 4 weeks. The exception is when Hb increases by more than 10 g/dl (10 g/l) in 2–4 weeks after initiation of therapy, at time the dose should be reduced by 25%–50% (Good practice statement)
▪️ 3.3.4: In people with anemia and CKD treated with ESA, it is reasonable to suspend ESA during hospitalization for acute stroke, vascular access thrombosis, or thromboembolic events. Individualize consideration for ESA reinitiation based on patient characteristics, Hb level, and preferences regarding risks and benefits of ESA treatment. (Good practice statement)
▪️ 3.3.5: We recommend exerting extreme caution while prescribing ESA therapy in CKD patients with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome. (Strong recommendation)
3.4: ESA Hyporesponsiveness
▪️ 3.4.1: In patients with anemia and (CKD- HD) or anemia (CKD-ND) not receiving dialysis with initial or subsequent ESA hyporesponsiveness, identify and treat the underlying causes of ESA hyperresponsiveness, if possible (Good practice statement)
CHAPTER 4. NOVEL ANEMIA THERAPIES: HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITORS HIF-PHIS
4.1: Treatment Initiation and Maintenance
▪️ 4.1.1: Do not use ESAs and HIF-PHIs in combination in people with anemia and CKD, including those with ESA hyporesponsiveness, (Good Practice Statement)
▪️ 4.1.2: In CKD patients with anemia, and ESA hyporesponsiveness, if there is a desire to raise the Hb to avoid a transfusion or improve symptoms attributable to anemia, a trial of HIF-PHI if available may be considered after discussion of potential risks and benefits prior to treatment if available (Good practice Statement)
▪️ 4.1.3: In CKD patients with anemia, if a decision is made to use HIF-PHI for the treatment of ESA hyporesponsiveness, the Hb should be raised to the lowest level that alleviates anemia-related symptoms or which reduces the risk of requiring RBC transfusion (Good practice Statement)
▪️ 4.1.4: In CKD patients with anemia, and ESA hyporesponsiveness, if a desired erythropoietic response has not been achieved after 3–4 months of initiating a trial of HIF-PHI, discontinue treatment (Good practice Statement)
▪️ 4.1.5.: In people with anemia and CKD, the Hb thresholds for the initiation and maintenance of HIF-PHIs are unknown, but it is reasonable to use the same Hb thresholds as those recommended or suggested for ESA therapy. (Good Practice Statement)
▪️ 4.1.6: In people with anemia and CKD, dose HIF-PHIs according to the recommended starting doses. (Good Practice Statement)
▪️ 4.1.7: In CKD patients with anemia, administer HIF-PHIs at the lowest dose needed to improve symptoms of anemia and to avoid RBC transfusions. (Good Practice Statement)
▪️ 4.1.8 Do not escalate HIF-PHI doses beyond the recommended maximum dose in people with anemia and CKD. (Good practice statement)
4.2: HIF-PHI Treatment Initiation and Maintenance
▪️ 4.2.1: In people with anemia and CKD, when dosing HIF-PHIs, monitor the Hb levels 2–4 weeks after initiation or dose changes and subsequently, every 4 weeks during therapy. (Good Practice Statement)
▪️ 4.2.2: In people with anemia and CKD, discontinue HIF-PHI after 3–4 months if a desired erythropoietic response has not been achieved. (Good Practice Statement)
▪️ 4.2.3: In people with anemia and CKD, suspend treatment with HIF-PHIs in those who experience cardiovascular events (e.g., stroke, myocardial infarction); thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism); vascular access thrombosis; or newly diagnosed cancer. (Good Practice Statement)
CHAPTER 5. RED BLOOD CELL TRANSFUSION TO TREAT ANEMIA IN PEOPLE WITH CKD
5.1: Red blood Cell Transfusion in Chronic Anemia
▪️ 5.1: In patients with anemia of CKD, especially those in whom renal transplantation is an option, red blood cell transfusion is better avoided unless life saving condition, prefrabially transfer washed irritated RBCs if available, to minimize the risk of allosensitisation (Conditional Recommendation)
▪️ 5.2: In people with CKD and chronic anemia, consider that the benefits of RBC transfusions may outweigh its harms in people in whom:
o ESA or HIF-PHI therapy is ineffective (e.g., hemoglobinopathies, bone marrow failure, ESA or HIF-PHI resistance)
o E SA or HIF-PHI therapy is harmful (e.g., previous or current malignancy, previous stroke)
o In life threatening conditions
(Good Practice Statement)
▪️ 5. 3: In patients with CKD and acute anemia consider red blood cell transfusion in patients with CKD and acute anemia when the benefits outweigh the risks, including:
o When rapid correction of anemia is required to stabilize the patient's condition (e.g., acute hemorrhage, unstable coronary artery disease), and
o When rapid preoperative Hb correction is required.
(Good Practice Statement)
▪️ 5.4: In people with anemia and CKD, the decision to transfusion should be based on symptoms and signs caused by anemia rather than an arbitrary Hb threshold. (Good Practice Statement)
▪️ 5.1.5: Consider implementing strategies at the individual, organizational, and public health policy levels to reduce RBC transfusions in people with CKD. (Good Practice Statement)
