Guideline 3.1- Investigations Before Initiating ESA Therapy:
We recommend that all correctable causes of anaemia should be ruled out before considering treatment with ESAs. (1B)
Guideline 3.2 – Treatment of Anaemia with Iron Therapy – Initiation of ESA and Iron Status:
We recommend that ESA therapy should NOT be initiated in the presence of absolute iron deficiency, (ferritin <100 mcg/L in people with non-dialysis dependent CKD (NDD-CKD) and <200 mcg/L in people who are dialysis dependent) until this is corrected and it is determined that anaemia persists, in conjunction with a shared decision of the advantages and risks of ESA therapy. In people with functional iron deficiency, iron supplements should be given prior to or when initiating ESA therapy. (1B)
Guideline 3.3 – Treatment of Anaemia – Erythropoiesis Stimulating Agents:
We recommend that treatment with ESAs should be offered to people with anaemia of CKD, in conjunction to a shared decision of the advantages and risks, who are likely to benefit in terms of quality of life and physical function and to avoid blood transfusion; especially in people considered suitable for transplantation. (1B)
Guideline 3.4 – Treatment of Anaemia with ESA therapy – Target Haemoglobin Range:
We recommend that people with non-dialysis dependent CKD (NDD-CKD) or those receiving dialysis, who are on ESA therapy, should achieve Hb between:
- 100 and 120 g/L in adults, young people and children aged 2 years and older. (1B)
- 95 and 115 g/L in children younger than 2 years of age (reflecting the lower normal range in that age). (2B)
Guideline 3.5 – Treatment of Anaemia without ESA Therapy – Target Haemoglobin Range:
We suggest that this Hb target range applies exclusively to people with CKD receiving ESAs and is not intended to apply to the treatment of iron deficiency in people receiving iron therapy without the use of ESAs. (2B)
Guideline 3.6 – Treatment of Anaemia – Choice of ESA:
We recommend that the choice of ESA is based on local availability and cost of ESAs. (1B)
Guideline 3.7 – Treatment of Anaemia – Initial ESA Dose:
We suggest that the initial ESA dose should be determined by the individual’s Hb level, the desired target Hb range, the observed rate of increase in Hb level and clinical circumstances. (2B)
Guideline 3.8 – Treatment of Anaemia with ESA Therapy – Route of Administration:
We suggest that the route of ESA administration should be determined by the CKD grade, individual recipient preference, treatment setting, efficacy, safety and class of ESA used. Subcutaneous (SC) use is preferable in people who are not receiving HD to avoid puncture of peripheral veins. Subcutaneous administration of short-acting ESA preparations may be preferred in people receiving haemodialysis due to improved ESA efficacy at the EPO receptor, allowing for smaller doses to be used. However, convenience and choice may favour intravenous (IV) administration in people on HD. (2B)
Guideline 3.9 – Treatment of Anaemia with ESA Therapy – Frequency of Administration:
We suggest that the frequency of administration should be determined by the CKD grade, person preference, treatment setting and class of ESA. Less frequent administration using long-acting ESAs may be the treatment of choice in people with CKD not on haemodialysis. (2B)
Guideline 3.10 – Treatment of Anaemia with ESA Therapy – ESA Dose Adjustments:
We recommend that adjustments to ESA doses should be considered when Hb is <105 or >115 g/L in adults, young people and children aged 2 years and older (1A)
Guideline 3.10.1
We suggest these thresholds for intervention should achieve a population distribution centered on a mean of 110 g/L with a range of 100-120 g/L. (2B)
Guideline 3.10.2
We suggest in children younger than 2 years to keep the Hb level within the aspirational range, do not wait until Hb levels are outside the aspirational range before adjusting treatment (for example, take action when Hb levels are within 5 g/L of the range’s limits). (not graded)
Guideline 3.10.3
We suggest that ESA doses should ideally be decreased rather than withheld when a downward adjustment of Hb level is desirable. (2B)
Guideline 3.11 – Treatment of Anaemia with ESA Therapy – Specific Situations:
We suggest that ESA administration in ESA-dependent people should continue during acute illness, surgical procedure or any other cause of hospitalisation, unless there is a clear contra-indication (for example, acute stroke or vascular access thrombosis). (2B)
Guideline 3.12 – Caution in Prescribing ESA in Certain People with CKD:
We suggest exerting caution while prescribing ESA therapy in people with CKD with a history of stroke, or malignancy, particularly in those with active malignancy when cure is the anticipated outcome. (2C)
Guideline 3.13 – Monitoring of ESA Treatment – Haemoglobin during ESA Therapy:
We suggest that Hb concentration should be monitored every 2-4 weeks in the correction phase or after a dose adjustment and every 1-3 months for stable individuals in the maintenance phase of ESA treatment. More frequent monitoring will depend on clinical circumstances. (2B)
Guideline 3.14 – Monitoring of ESA Treatment – Resistance to ESA Therapy:
We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the target Hb range despite SC epoetin dose >300 IU/kg/week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 mcg/kg/week, or equivalent dose of methoxy ethylene glycol epoetin beta following investigation and treatment of other causes. (1A)
Guideline 3.14.1
We suggest that clinicians consider accepting lower aspirational haemoglobin target ranges in those on high, escalating ESA doses with inadequate response, or consider alternative therapy such as a trial use of HIF-PHI. (2C)
Guideline 3.15 – Monitoring of ESA Treatment – Evaluation for ESA Induced Pure Red Cell Aplasia: We recommend that a diagnosis of ESA-induced pure red cell aplasia (PRCA) should be considered whenever a person receiving long-term ESA therapy (>8 weeks) develops all the following (1A):
- A sudden decrease in Hb concentration at the rate of 5 to 10 g/L per week or requirement of transfusions at the rate of approximately 1 to 2 per week
- Normal platelet and white cell counts
- Absolute reticulocyte count less than 10,000/μl
- High serum ferritin level
Guideline 3.15.1
We recommend that all ESA therapy should be stopped in people who develop ESA-induced PRCA. (1A)
Guideline 3.15.2
We recommend that individuals who remain transfusion dependent after withdrawing ESA therapy should be treated with immunosuppressant medications guided by the level of anti EPO antibodies. (1B)
Guideline 3.15.3
We do not recommend routine screening for anti-erythropoietin antibodies among people with CKD regularly treated with ESAs. (1B)
Guideline 3.16 – Monitoring of ESA treatment – Hypertension during ESA therapy:
We recommend that blood pressure should be monitored in all people receiving ESAs and, if present, hypertension be treated by volume removal and/or antihypertensive drugs. (1A)