1 Recommendations

The following guidance is based on the best available evidence. The full guideline gives details of the methods and the evidence used to develop the guidance.

The wording used in the recommendations in this guideline (for example, words such as 'offer' and 'consider') denotes the certainty with which the recommendation is made (the strength of the recommendation). See about this guideline for details.

1.1 Diagnostic evaluation and assessment of anaemia

Diagnostic role of haemoglobin levels

1.1.1 Consider investigating and managing anaemia in people with chronic kidney disease (CKD) if:

  • their haemoglobin (Hb) level falls to 110 g/litre or less (or 105 g/litre or less if younger than 2 years) or

  • they develop symptoms attributable to anaemia (such as tiredness, shortness of breath, lethargy and palpitations). [2011]

Diagnostic role of glomerular filtration rate

1.1.2 An estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73m2 should trigger investigation into whether anaemia is due to CKD. When the eGFR is greater than or equal to 60 ml/min/1.73 m2 the anaemia is more likely to be related to other causes. [2006]

Diagnostic tests to determine iron status and predict response to iron therapy

1.1.3 Carry out testing to diagnose iron deficiency and determine potential responsiveness to iron therapy and long‑term iron requirements every 3 months (every 1–3 months for people receiving haemodialysis).

  • Use percentage of hypochromic red blood cells (% HRC; more than 6%), but only if processing of blood sample is possible within 6 hours.

  • If using percentage of hypochromic red blood cells is not possible, use reticulocyte Hb content (CHr; less than 29 pg) or equivalent tests – for example, reticulocyte Hb equivalent.

  • If these tests are not available or the person has thalassaemia or thalassaemia trait, use a combination of transferrin saturation (less than 20%) and serum ferritin measurement (less than 100 micrograms/litre). [new 2015]

1.1.4 Do not request transferrin saturation or serum ferritin measurement alone to assess iron deficiency status in people with anaemia of CKD. [new 2015]

Measuring erythropoietin

1.1.5 Do not routinely consider measurement of erythropoietin levels for the diagnosis or management of anaemia in people with anaemia of CKD. [2006]

1.2 Managing anaemia

Initiation of ESA therapy in iron‑deficient patients

1.2.1 ESA (erythropoietic stimulating agent) therapy should not be initiated in the presence of absolute iron deficiency without also managing the iron deficiency. [2006]

Maximum iron levels in people with anaemia of CKD

1.2.2 In people treated with iron, serum ferritin levels should not rise above 800 micrograms/litre. In order to prevent this, review the dose of iron when serum ferritin levels reach 500 micrograms/litre. [2006]

Clinical utility of ESA therapy in iron‑replete patients

1.2.3 The pros and cons of a trial of anaemia management should be discussed between the clinician, the person with anaemia of CKD, and their families and carers if applicable. [2006]

1.2.4 ESAs need not be administered where the presence of comorbidities, or the prognosis, is likely to negate the benefits of correcting the anaemia. [2006]

1.2.5 Initiate a trial of anaemia correction when there is uncertainty over whether the presence of comorbidities, or the prognosis, would negate benefit from correcting the anaemia with ESAs. [2006]

1.2.6 Where a trial of ESA therapy has been performed, assess the effectiveness of the trial after an agreed interval. Where appropriate, a mutual decision should be agreed between the clinician, the person with anaemia of CKD and their families and carers on whether or not to continue ESA therapy. [2006]

1.2.7 Review all people started on ESA therapy after an agreed interval in order to decide whether or not to continue using ESAs. [2006]

Nutritional supplements

1.2.8 Supplements of vitamin C, folic acid or carnitine should not be prescribed as adjuvants specifically for the treatment of anaemia of CKD. [2006]

Androgens

1.2.9 In people with anaemia of CKD, androgens should not be used to treat the anaemia. [2006]

Hyperparathyroidism

1.2.10 In people with anaemia of CKD, treat clinically relevant hyperparathyroidism to improve the management of the anaemia. [2006]

Patient‑centred care: ESAs

1.2.11 Give people offered ESA therapy and their GPs information about why ESA therapy is required, how it works and what benefits and side effects may be experienced. [2006]

1.2.12 When managing the treatment of people with anaemia of CKD, there should be agreed protocols defining roles and responsibilities of healthcare professionals in primary and secondary care. [2006]

1.2.13 Inform people receiving ESA therapy about the importance of concordance with therapy and the consequences of poor concordance. [2006]

1.2.14 When prescribing ESA therapy, take into account patient preferences about supervised‑ or self‑administration, dose frequency, pain on injection, method of supplying ESA and storage. [2006]

1.2.15 In order for people to self‑administer their ESA in a way that is clinically effective and safe, make arrangements to provide ready, reasonable and uninterrupted access to supplies. [2006]

Patient education programmes

1.2.16 Offer culturally and age‑appropriate patient education programmes to all people diagnosed with anaemia of CKD (and their families and carers). These should be repeated as requested, and according to the changing circumstances of the patient. They should include the following key areas:

  • Practical information about how anaemia of CKD is managed.

  • Knowledge (for example, about symptoms, iron management, causes of anaemia, associated medications, phases of treatment).

  • Professional support (for example, contact information, community services, continuity of care, monitoring, feedback on progress of results).

  • Lifestyle (for example, diet, physical exercise, maintaining normality, meeting other patients).

  • Adaptation to chronic disease (for example, previous information and expectations, resolution of symptoms). [2006]

1.3 Assessment and optimisation of erythropoiesis

Benefits of treatment with ESAs

1.3.1 Offer treatment with ESAs to people with anaemia of CKD who are likely to benefit in terms of quality of life and physical function. [2006]

Blood transfusions

1.3.2 Avoid blood transfusions where possible in people with anaemia of CKD in whom kidney transplant is a treatment option. [2006]

1.3.3 In people with anaemia of CKD, there may be situations where a transfusion is indicated clinically. In these cases, follow the relevant national guidance[7]. [2006, amended 2015]

Comparisons of ESAs

1.3.4 Discuss the choice of ESA with the person with anaemia of CKD when initiating treatment and at subsequent review, taking into consideration the patient's dialysis status, the route of administration and the local availability of ESAs. There is no evidence to distinguish between ESAs in terms of efficacy. [2006]

Coordinating care

1.3.5 People with anaemia of CKD should have access to a designated contact person or persons who have principal responsibility for their anaemia management and who have skills in the following activities:

  • Monitoring and managing a caseload of patients in line with locally agreed protocols.

  • Providing information, education and support to empower patients and their families and carers to participate in their care.

  • Coordinating an anaemia service for people with CKD, working between secondary and primary care and providing a single point of contact, to ensure patients receive a seamless service of the highest standard.

  • Prescribing medicines related to anaemia management and monitoring their effectiveness. [2006]

Providing ESAs

1.3.6 ESA therapy should be clinically effective, consistent and safe in people with anaemia of CKD. To achieve this, the prescriber and patient should agree a plan that is patient‑centred and includes: 

  • continuity of drug supply

  • flexibility of where the drug is delivered and administered

  • the lifestyle and preferences of the patient

  • cost of drug supply

  • desire for self‑care where appropriate

  • regular review of the plan in light of changing needs. [2006]

ESAs: optimal route of administration

1.3.7 The person with anaemia of CKD and the prescriber should agree (and revise as appropriate) the route of administration of ESAs, taking into account the following factors:

  • patient population (for example, haemodialysis patients)

  • pain of injection

  • frequency of administration

  • the lifestyle and preferences of the patient

  • efficacy (for example, subcutaneous versus intravenous administration, or long‑acting versus short‑acting preparations)

  • cost of drug supply. [2006]

1.3.8 The prescriber should take into account that when using short‑acting ESAs, subcutaneous injection allows the use of lower doses of drugs than intravenous administration. [2006]

ESAs: dose and frequency

1.3.9 When correcting anaemia of CKD, the dose and frequency of ESA should be:

  • determined by the duration of action and route of administration of the ESA

  • adjusted to keep the rate of Hb increase between 10 and 20 g/litre/month. [2006]

Optimal Hb levels

1.3.10 When determining individual aspirational Hb ranges for people with anaemia of CKD, take into account:

  • patient preferences

  • symptoms and comorbidities

  • the required treatment. [2011]

1.3.11 The correction to normal levels of Hb with ESAs is not usually recommended in people with anaemia of CKD.

  • Typically maintain[8] the aspirational Hb range between 100 and 120 g/litre for adults, young people and children aged 2 years and older, and between 95 and 115 g/litre for children younger than 2 years of age, reflecting the lower normal range in that age group.

  • 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/litre of the range's limits). [2011, amended 2015]

1.3.12 Consider accepting Hb levels below the agreed aspirational range if:

  • high doses[9] of ESAs are required to achieve the aspirational range or

  • the aspirational range is not achieved despite escalating ESA doses. [2011]

1.3.13 Age alone should not be a determinant for treatment of anaemia of CKD. [2006]

Adjusting ESA treatment

1.3.14 Optimise iron status before or coincident with the initiation of ESA administration and during maintenance treatment with ESAs. [2006, amended 2011]

1.3.15 Use of angiotensin‑converting enzyme (ACE) inhibitors or angiotensin type II receptor antagonists is not precluded, but if they are used, an increase in ESA therapy should be considered. [2006]

1.3.16 Take into account Hb measurements when determining the dose and frequency of ESA administration.

  • Investigate the cause of an unexpected change in Hb level (that is, intercurrent illness, bleeding) to enable intervention and optimise iron status.

  • Increase or decrease ESA dose and/or frequency when Hb measurements fall outside action thresholds (usually below 105 g/litre or above 115 g/litre), or for example when the rate of change of Hb suggests an established trend (for example, greater than 10 g/litre/month). [2006, amended 2011]

Treating iron deficiency: correction

1.3.17 Offer people with anaemia of CKD who are receiving ESAs iron therapy to achieve[10]:

  • percentage of hypochromic red blood cells less than 6% (unless ferritin is greater than 800 micrograms/litre)

  • reticulocyte Hb count or equivalent tests above 29 pg (unless serum ferritin is greater than 800 micrograms/litre).

    If the above tests are not available or the person has thalassaemia or thalassaemia trait, iron therapy should maintain transferrin saturation greater than 20% and serum ferritin level greater than 100 micrograms/litre (unless serum ferritin is greater than 800 micrograms/litre).

    Most patients will need 500–1000 mg of iron for adults or equivalent doses for children[11], in a single or divided dose depending on the preparation. Intravenous iron should be administered in a setting with facilities for resuscitation. [new 2015]

Treating iron deficiency: maintenance

1.3.18 Once percentage of hypochromic red blood cells is less than 6%, reticulocyte Hb count or equivalent tests are above 29 pg, or transferrin saturation is greater than 20% and serum ferritin level is greater than 100 micrograms/litre, offer maintenance iron to people with anaemia of CKD who are receiving ESAs.

The dosing regimen will depend on modality, for example haemodialysis patients will need the equivalent of 50–60 mg intravenous iron per week (or an equivalent dose in children[11] of 1 mg/kg/week). [new 2015]

ESAs: monitoring iron status during treatment

1.3.19 Offer iron therapy to people[11] receiving ESA maintenance therapy to keep their[10]:

  • percentage of hypochromic red blood cells less than 6% (unless serum ferritin is greater than 800 micrograms/litre)

  • reticulocyte Hb count or equivalent tests above 29 pg (unless serum ferritin is greater than 800 micrograms/litre)

  • transferrin saturation level above 20% and serum ferritin level above 100 micrograms/litre (unless serum ferritin is greater than 800 micrograms/litre).

    The marker of iron status should be monitored every 1–3 months in people receiving haemodialysis.

    In people who are pre‑dialysis[12] or receiving peritoneal dialysis, levels are typically monitored every 3 months. If these people have a normal full blood count there is little benefit in checking iron status. [new 2015]

Iron therapy for people who are iron deficient and not on ESA therapy

1.3.20 Offer iron therapy to people[11] with anaemia of CKD who are iron deficient and who are not receiving ESA therapy, before discussing ESA therapy.

  • Discuss the risks and benefits of treatment options. Take into account the person's choice.

  • For people who are not receiving haemodialysis, consider a trial of oral iron before offering intravenous iron therapy. If they are intolerant of oral iron or target Hb levels are not reached within 3 months (see recommendation 1.3.11), offer intravenous iron therapy.

  • For people who are receiving haemodialysis, offer intravenous iron therapy. Offer oral iron therapy to people who are receiving haemodialysis only if:

    • intravenous iron therapy is contraindicated or

    • the person chooses not to have intravenous iron therapy after discussing the relative efficacy and side effects of oral and intravenous iron therapy. [new 2015]

1.3.21 Discuss the results of the iron therapy with the person or, where appropriate, with their family or carers and offer ESA therapy if needed (see recommendation 1.3.1). [new 2015]

Iron therapy for people who are iron deficient and receiving ESA therapy

1.3.22 Offer iron therapy to people[11] with anaemia of CKD who are iron deficient and who are receiving ESA therapy.

  • Discuss the risks and benefits of treatment options. Take into account the person's choice.

  • For adults and young people, offer intravenous iron therapy.

  • For children who are receiving haemodialysis, offer intravenous iron therapy.

  • For children who are not receiving haemodialysis, consider oral iron. If the child is intolerant of oral iron or target Hb levels are not reached within 3 months (see recommendation 1.3.11), offer intravenous iron therapy. [new 2015]

1.3.23 Offer oral iron therapy to adults and young people who are receiving ESA therapy only if:

  • intravenous iron therapy is contraindicated or

  • the person chooses not to have intravenous iron therapy after discussing the relative efficacy and side effects of oral and intravenous iron therapy. [new 2015]

1.3.24 When offering intravenous iron therapy to people not receiving haemodialysis, consider high‑dose low‑frequency[13] intravenous iron as the treatment of choice for adults and young people when trying to achieve iron repletion. Take into account all of the following:

  • preferences of the person with anaemia of CKD or, where appropriate, their family or carers

  • nursing and administration costs

  • cost of local drug supply

  • provision of resuscitation facilities.

    Intravenous iron administered at a low dose and high frequency[14] may be more appropriate for all children[11] and for adults who are receiving in‑centre haemodialysis. [new 2015]

1.4 Monitoring treatment of anaemia of CKD

Monitoring iron status

1.4.1 People with anaemia of CKD should not have iron levels checked earlier than 1 week after receiving intravenous iron. The length of time to monitoring of iron status is dependent on the product used and the amount of iron given. [2006]

1.4.2 Routine monitoring of iron stores to prevent iron overload using serum ferritin should be at intervals of 1–3 months. [2006, amended 2015]

Monitoring Hb levels

1.4.3 In people with anaemia of CKD, monitor Hb:

  • every 2–4 weeks in the induction phase of ESA therapy

  • every 1–3 months in the maintenance phase of ESA therapy

  • more actively after an ESA dose adjustment

  • in a clinical setting chosen in discussion with the patient, taking into consideration their convenience and local healthcare systems. [2006]

Detecting ESA resistance

1.4.4 After other causes of anaemia, such as intercurrent illness or chronic blood loss have been excluded, people with anaemia of CKD should be considered resistant to ESAs when:

  • an aspirational Hb range is not achieved despite treatment with 300 IU/kg/week or more of subcutaneous epoetin or 450 IU/kg/week or more of intravenous epoetin or 1.5 micrograms/kg/week of darbepoetin or

  • there is a continued need for the administration of high doses of ESAs to maintain the aspirational Hb range. [2006]

1.4.5 In people with CKD, pure red cell aplasia (PRCA) is indicated by a low reticulocyte count, together with anaemia and the presence of neutralising antibodies. Confirm PRCA by the presence of anti‑erythropoietin antibodies together with a lack of pro‑erythroid progenitor cells in the bone marrow. [2006]

1.4.6 In people with anaemia of CKD, aluminium toxicity should be considered as a potential cause of a reduced response to ESAs after other causes, such as intercurrent illness and chronic blood loss, have been excluded. [2006]

Managing ESA resistance

1.4.7 In haemodialysis patients with anaemia of CKD in whom aluminium toxicity is suspected, perform a desferrioxamine test and review the patient's management accordingly. [2006]

1.4.8 Consider specialist referral for ESA‑induced PRCA. [2006, amended 2011]

Role of blood transfusion in managing ESA resistance

1.4.9 Consider referring people with ESA resistance to a haematology service, particularly if an underlying haematological disorder is suspected. [new 2015]

1.4.10 Evaluate and discuss the risks and benefits of red cell transfusion with the person or, where appropriate, with their family or carers. [new 2015]

1.4.11 Take into account the person's symptoms, quality of life, underlying conditions and the chance of a future successful kidney transplant, in addition to Hb levels, when thinking about the need for red cell transfusion. [new 2015]

1.4.12 Review the rate of red cell transfusion and consider a trial period of stopping ESA in people who have ESA resistance (typically on haemodialysis and on high‑dose ESA) and are having frequent transfusions when:

  • all reversible causes of ESA resistance have been taken into account and excluded and

  • the person's condition is otherwise 'stable' (without intercurrent illness such as infection) and

  • the person is receiving adequate dialysis.

    Review the rate of red cell transfusion between 1 and 3 months after stopping ESA therapy. If the rate of transfusion has increased, consider restarting ESA therapy. [new 2015]



[7] NICE is developing the guideline 'Blood transfusion' (publication expected November 2015).

[8] The Medicines and Healthcare products Regulatory Agency (MHRA) guidance (2007) notes that using ESAs to achieve Hb levels greater than 120 g/litre is associated with an increased risk of death and serious cardiovascular events in people with CKD. The MHRA advises that Hb levels greater than this should be avoided, and that patients should be monitored closely to ensure that the lowest approved dose of ESA is used to provide adequate control of the symptoms of anaemia. Use of ESAs to achieve Hb levels greater than 120 g/litre is not consistent with UK marketing authorisations for ESAs. If such use is considered, the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information.

[9] More than 175 international units per kg per week for haemodialysis population; more than 125 international units per kg per week for peritoneal dialysis population; more than 100 international units per kg per week for non-dialysis population. (Data provided by the UK Renal Registry and Guideline Development Group expert opinion.)

[10] See recommendation 1.1.3 for tests of choice to determine iron deficiency.

[11] Refer to the Summary of Product Characteristics for the prescription of individual iron preparations. At the time of publication (June 2015), intravenous iron products available in the UK did not have a UK marketing authorisation for all ages of children and young people for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information. Note that the marketing authorisation for ferumoxytol in the EU was withdrawn by the manufacturer in March 2015.

[12] There is no accepted definition of pre‑dialysis. It is usually regarded to be CKD stages 4 and 5. Pre‑dialysis includes people with a failing transplant and people having conservative management.

[13] The Guideline Development Group (GDG) considered this to be a maximum of 2 infusions. For adults, the GDG considered there would be a minimum of 500 mg of iron in each infusion. Refer to the Summary of Product Characteristics for the prescription of individual iron preparations.

[14] The Guideline Development Group (GDG) considered this to be more than 2 infusions. For adults, the GDG considered there would typically be 100–200 mg of iron in each infusion. Refer to the Summary of Product Characteristics for the prescription of individual iron preparations.

  • National Institute for Health and Care Excellence (NICE)