Education: Anaemia in Renal Disease

Education: Anaemia in Renal Disease

 

Renal anaemia is a normochromic normocytic anaemia that increases in severity as renal function declines. There are a number of explanations for anaemia in patients with renal failure, but relative deficiency of erythropoietin (EPO) is usually dominant when patients are nearing end-stage.

EPO is a hormone produced by the kidneys in response to an anaemic hypoxic stimulus; it acts to correct anaemia by stimulating red cell production in the bone marrow. Anaemia due to EPO deficiency can occur with any stage of CKD, but does not usually develop until eGFR is less than 30ml/min/1.73m2  (<45/min/1.73m2 in patients with diabetes) and worsens with declining renal function. The majority of patients who require renal replacement therapy will require EPO replacement.

Other causes of anaemia in patients with renal failure include:

  • Reduced red blood cell lifespan
  • Uraemic inhibition of erythropoiesis
  • Cytokine inhibition of erythopoiesis, e.g. during infections and in inflammatory disorders
  • Iron deficiency and disordered iron utilisation
  • Active blood loss (including circuit loss during haemodialysis treatments)
  • Nutritional deficiencies, e.g. B12 and folate deficiency

Without effective treatments anaemia can be very severe and there is a strong association between low haemoglobin and risk of death in ESRF (reference). Improving haemoglobin by use of erythropoiesis-stimulating agents (ESAs) results in improvements in exercise tolerance, quality of life, cognitive function, immune-responsiveness, nutrition, sleep patterns and cardiac status (including reduce left ventricular hypertrophy and dilatation)(reference).

However, whilst you might assume that restoring haemoglobin to within a normal range would be most beneficial, clinical trials have not supported this practice due to an increased risk of thrombosis (including stroke), and other adverse effects due to the presence of EPO receptors on cells outwith the bone marrow (reference). Target haemoglobin for patients receiving ESAs is therefore low-normal, usually between 100 and 120g/L (reference).

Baseline Investigations

In accordance with the Renal Association Clinical Practice Guideline 2017 we would recommend the following investigations for patients with CKD who are found to be anaemic, these are similar to those investigations you would perform for patients without CKD. 

Full blood count
  • Mean corpuscular haemoglobin [MCH]
  • Mean corpuscular volume [MCV]
  • White blood cell count and differential
  • Platelet count
  • Reticulocyte count to assess bone marrow responsiveness
Iron status
  • Serum ferritin
  • Transferrin saturation (TSAT)
Haematinics
  • Serum B12 and Folate concentrations
Inflammation
  • CRP
Haemolysis screen
  • Haptoglobin
  • Lactate dehydrogenase (LDH)
  • Bilirubin
  • Direct Coomb’s test
Exclude myeloma / paraproteinaemia
  • Plasma and/or urine protein electrophoresis
  • Serum free light chains (SFLC) and bone marrow examination

Based on the results of the above investigations, a decision can me made as to whether or not anaemia is related purely to EPO deficiency, or whether there are additional contributory factors which require alternative treatment.

References

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