24th June 2023

Anaemia

Mechanism

The healthy kidneys normally produce erythropoietin (EPO) in response to cell hypoxia, this stimulates bone marrow red blood cell production. Reduced production in chronic kidney disease results in less erythropoiesis and a normochromic normocytic anaemia.

However, renal patients are also at risk of other causes of anaemia, with iron deficiency commonly seen. Iron deficiency can be absolute (reduced stores) or functional (normal stores but inability to use).

• Absolute – due to gastrointestinal losses (uraemic platelet dysfunction increases the risk of bleeding), serial phlebotomy, circuit clotting during haemodialysis, or reduced absorption due to medication such as acid inhibitors and phosphate binders.
• Functional – due to underlying inflammation preventing the body from using stored iron (haemodialysis itself is a pro-inflammatory state due to interaction with the dialysis membrane), high hepcidin levels (increased in inflammatory states, decreased renal clearance) also reduces the body’s ability to absorb and use iron.

Investigation

• Full blood count – target haemoglobin (Hb) in CKD is 100-120g/L (higher levels are linked with an increased risk of cardiovascular disease). Review the mean corpuscular volume and the mean cell haemoglobin concentration; anaemia related to reduced EPO alone should be normochromic and normocytic.
• Serum ferritin level (target of 200-500 μg/l in haemodialysis patients and 100-500μg/l in CKD patients not on dialysis) and transferrin saturations (target of >20%) – targets from the UK Renal Association
• Serum B12 and folate levels

Management

• Iron replacement – it should be ensured that a patient is iron-replete before considering erythropoiesis-stimulating agents. The intravenous route is preferable to oral, especially in more advanced CKD/haemodialysis patients, though this does carry a small but significant risk of drug reaction.
• Erythropoiesis-stimulating agents – recombinant erythropoietin addresses the lack of endogenous production; it can be given subcutaneously or intravenously. Notable cautions/contraindications include pure red cell aplasia, uncontrolled hypertension, intercurrent infection, malignancy, or other inflammatory disease.
• Red cell transfusion – generally avoided. The risks and benefits of transfusion need to be considered carefully in patients who may be eligible for a renal transplant, as antibody formation may limit future organ matching options.