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1. Evaluating and Diagnosing Anaemia in CKD (Guidelines 1.1 – 1.5)
Guideline 1.1 – Evaluation of anaemia - Screening for anaemia
We suggest that haemoglobin (Hb) levels should be routinely measured to screen for anaemia:
at least annually in patients with CKD G3 and
at least twice a year in patients with CKD G4-5 not on dialysis (2B)
Guideline 1.2 - Evaluation of anaemia – haemoglobin levels
We recommend that all patients with chronic anaemia associated with chronic kidney disease (CKD) should be investigated for the cause and possible treatment, irrespective of the grade of kidney disease or requirement for renal replacement therapy if:
their haemoglobin (Hb) levels are less than 110g/L (less than 105 g/L if younger than 2 years) or
they develop symptoms attributable to anaemia
This is to ensure the correct diagnosis and management of anaemia. (1A)
Guideline 1.3 - Evaluation of anaemia - Renal function
We suggest that CKD should be considered as a possible cause of anaemia 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 (<45/min/1.73m2 in patients with diabetes) and no other cause, e.g. blood loss, folic acid or vitamin B12 deficiency, is identified. (2B)
Guideline 1.4 - Evaluation of anaemia - Erythropoietin measurement
We recommend that measurement of erythropoietin levels should not routinely be considered for the diagnosis or management of anaemia for patients with CKD. (1A)
Guideline 1.5 - Evaluation of anaemia – Baseline investigations
We recommend that initial clinical and laboratory evaluation of anaemia should be performed prior to initiation of treatment for anaemia in CKD patients. (1A)
We recommend that laboratory evaluation should include the following tests (1B):
Full blood count (FBC) including—in addition to the Hb concentration:
red blood cell indices:
mean corpuscular haemoglobin [MCH]
mean corpuscular volume [MCV]
mean corpuscular haemoglobin concentration [MCHC])
white blood cell count and differential count
platelet count
Absolute reticulocyte count to assess bone marrow responsiveness (if indicated).
Test to determine iron status:
percentage of hypochromic red blood cells (% HRC), but only if processing of blood sample is possible within 6 hours or
reticulocyte Hb count (CHr) or equivalent tests e.g. reticulocyte Hb equivalent or
combination of transferrin saturation (TSAT) and serum ferritin if the above tests are not available or the person has thalassemia or thalassemia trait
Serum ferritin to assess iron stores.
Plasma/serum C-reactive protein (CRP) to assess inflammation.
Based on the initial assessment we recommend in selected cases, the following tests may be useful to diagnose the cause of anaemia (1B):
Serum B12 and serum folate concentrations.
Tests for haemolysis (plasma/serum levels of haptoglobin, lactate dehydrogenase, bilirubin, Coombs’ test).
Plasma/serum and/or urine protein electrophoresis.
Hb electrophoresis.
Free light chains and bone marrow examination.
2. Treatment of Anaemia with Iron Therapy Anaemia of CKD (Guidelines 2.1 – 2.4)
Guideline 2.1 - Treatment of Anaemia with Iron therapy – Iron repletion
We recommend that patients should be iron replete to achieve and maintain target Hb whether receiving ESAs or not. (1B)
Iron repletion is usually defined as:
%HRC <6% / CHr >29 pg / ferritin and TSAT (>100 microgram/L and >20%).
For children, aim for a target ferritin level greater than 100 microgram/L for CKD patients on dialysis as well as CKD patients not on ESA therapy. (ungraded)
Guideline 2.2 - Treatment of Anaemia with Iron Therapy - Initiation of ESA and Iron Status:
We suggest that ESA therapy should not be initiated in the presence of absolute iron deficiency (ferritin <100 microgram/L) until this is corrected and anaemia persists. In patients with functional iron deficiency iron supplements should be given prior to or when initiating ESA therapy. (2B)
Low serum ferritin is a useful marker to diagnose absolute iron deficiency. Normal or high serum ferritin values (≥100 microgram/L) do not exclude iron deficiency, as it could be due to other causes as infection or inflammation.
Guideline 2.3 - Treatment of Anaemia with Iron therapy - Route of Administration:
We suggest that oral iron will, in general, be sufficient to maintain and may be sufficient to attain the Hb within targets in ESA treated CKD patients not yet requiring dialysis and in those on peritoneal dialysis (PD). (2B)
For CKD patients not requiring haemodialysis, 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 the need to initiate ESA therapy (2A).
In contrast most haemodialysis patients will require intravenous iron. (2A).
When offering intravenous iron therapy to people not receiving in-centre haemodialysis, consider high dose, low frequency (HD/LF) IV iron as the treatment of choice for adults and young people when trying to achieve iron repletion, taking into account all of the following:
the availability of venous access
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
Guideline 2.4 - Treatment of Anaemia with Iron therapy - Upper limit for iron therapy
We recommend that serum ferritin should not exceed 800 microgram/L in patients treated with iron, and to achieve this iron management should be reviewed when the ferritin is >500 microgram/L. (1B)
3. Treatment with Erythropoiesis Stimulating Agents (Guidelines 3.1 – 3.11)
Guideline 3.1 - Treatment of Anaemia - Erythropoiesis Stimulating Agents
We recommend that treatment with Erythropoiesis Stimulating Agents (ESAs) should be offered to patients with anaemia of CKD who are likely to benefit in terms of quality of life and physical function and to avoid blood transfusion; especially in patients considered suitable for transplantation. (1B)
Guideline 3.2 - Treatment of Anaemia - Choice of ESA
We recommend that the decision on the choice of ESA is based on local availability of ESAs. (1B)
Guideline 3.3 - Treatment of Anaemia with ESA therapy - Target Hb:
We suggest that patients with CKD on ESA therapy should achieve Hb between:
100 and 120 g/L in adults, young people and children aged 2 years and older (2B)
95 and 115 g/L in children younger than 2 years of age (reflecting the lower normal range in that age
Guideline 3.4 - Treatment of Anaemia without ESA therapy - Target Hb
We suggest that this Hb target range applies exclusively to patients receiving ESA and are not intended to apply to the treatment of iron deficiency in patients receiving iron therapy without the use of ESAs. (2B)
Guideline 3.5 - Treatment of Anaemia - Initial ESA dose
We recommend that the initial ESA dose should be determined by the patient's Hb level, the target Hb level, the observed rate of increase in Hb level and clinical circumstances. (2B)
Guideline 3.6 - Treatment of Anaemia with ESA therapy - Route of administration:
We suggest that the route of ESA administration should be determined by the CKD grade, treatment setting,efficacy, safety, and class of ESA used; subcutaneous (SC) route is the access of choice in non-haemodialysis patients, while convenience may favour intravenous (IV) administration in haemodialysis patients. (2B)
Guideline 3.7 - Treatment of Anaemia with ESA therapy - Frequency of administration
We suggest that the frequency of administration should be determined by the CKD grade, treatment setting and class of ESA. Less frequent administration using long acting ESAs may be the treatment of choice in non–haemodialysis patients. (2B).
Guideline 3.8 - 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, in order to balance the benefit and safety to patients given the current evidence base.
These thresholds for intervention should achieve a population distribution centred on a mean of 110 g/L with a range of 100-120 g/L. (2B)
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).
Guideline 3.9 - Treatment of Anaemia with ESA Therapy - ESA dose adjustments
We suggest that ESA doses should ideally be decreased rather than withheld when a downward adjustment of Hb level is desirable (2B)
Guideline 3.10 - Treatment of Anaemia with ESA Therapy
We suggest that ESA administration in ESA-dependent patients should continue during acute illness, surgical procedures or any other cause of hospitalisation, unless there is a clear contra-indication such as accelerated hypertension. (2B)
Guideline 3.11 – Caution in prescribing ESA in certain CKD patients sub-group:
We suggest 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. (2C)
4. Monitoring of Therapy (Guidelines 4.1 – 4.7)
Guideline 4.1 - Monitoring of treatment - Hb during ESA therapy
We suggest that 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.
More frequent monitoring will depend on clinical circumstances. (2B)
Guideline 4.2 - Monitoring of treatment - Iron therapy
We recommend regular monitoring of iron status (every 1-3 months) in patients receiving intravenous iron to avoid toxicity (2B): a serum ferritin consistently greater than 800 microgram/L with no evidence of inflammation (normal CRP) may be suggestive of iron overload. (1B)
Guideline 4.3 - Monitoring during Intravenous Iron Administration
We recommend that resuscitative medication and personnel trained to evaluate and resuscitate anaphylaxis should be present at each administration of intravenous iron. (1A)
Guideline 4.4 - Parenteral iron & infection:
We suggest avoiding parenteral iron therapy in patients with active infection (2B)
Guideline 4.5 - Monitoring of treatment - Resistance to ESA therapy
We recommend that inadequate response (‘resistance’) to ESA therapy is defined as failure to reach the target Hb level despite SC epoetin dose >300 IU/kg/week (450 IU/kg/week IV epoetin), or darbepoetin dose >1.5 microgram/kg/week. Hyporesponsive patients who are iron replete should be screened clinically and by investigations for other common causes of anaemia. (1A)
Guideline 4.6- Evaluation for ESA Induced Pure Red Cell Aplasia (PRCA)
We do not recommend routine screening for anti-erythropoietin antibodies among CKD patients regularly treated with erythropoiesis stimulating agents. (2A)
We recommend that the diagnosis of ESA induced PRCA should be considered whenever a patient receiving long term ESA therapy (more than 8 weeks) develops all the following (2A):
a sudden decrease in Hb concentration at the rate of 5 to 10g/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
We recommend that all ESA therapy should be stopped in patients who develop ESA induced PRCA. (2A)
We recommend that patients who remain transfusion dependent after withdrawing ESA therapy should be treated with immunosuppressant medications guided by the level of anti EPO antibodies. (2A)
Guideline 4.7 - Monitoring of treatment - Hypertension during ESA therapy
We recommend that blood pressure should be monitored in all patients receiving ESAs and, if present, hypertension be treated by volume removal and/or anti-hypertensive drugs. (1A)
5. Anaemia of CKD: Blood Transfusion (Guidelines 5.1 – 5.3)
Guideline 5.1 - Blood Transfusion
We recommend that in patients with anaemia of CKD, especially those in whom renal transplantation is an option, red blood cell transfusion should be avoided where possible to minimise the risk of allosensitisation. (1A)
Guideline 5.2 - Blood Transfusion
We recommend if red blood cell transfusion becomes essential (usually in the setting of acute blood loss, acute haemolysis or severe sepsis) transfusions should be based on policies set by local transfusion guidelines rather than Hb targets for ESA therapy in chronic anaemia of CKD. (1B)
Guidelines 5.3- Blood transfusion
We recommend that renal transplant recipients, or those on the transplant waiting list or patients on immunosuppressive therapy should receive only Hepatitis E negative blood components. (2B)
6. Anaemia of CKD: Post Transplant Anaemia (Guideline 6.1)
We suggest that the treatment guidelines for anaemia in renal transplant patients should be similar to those for CKD patients not on dialysis. (2B)