Anaemia in Chronic Kidney Disease

Introduction

Anaemia is diagnosed in adults and children >15 years when the haemoglobin concentration is <13 g/dL in males and <12 g/dL in females.

The anaemia in ESRD patients normally presents as normocytic anaemia (normal MCV and MCHC) due to erythropoietin deficiency.

Prevalence: 26% of patients with a GFR greater than 60 ml/minute/1.73 m2 have anaemia, compared with 78% of patients with a GFR less than 15 ml/minute/1.73 m2.



Management

Treatment encompasses identifying and correcting the underlying causes of anaemia. Several factors are responsible for anaemia in CKD:

  • Decreased erythropoietin production (most important)
  • Decrease in RBC life span caused by uraemia and effects of "uremic inhibitors" on bone marrow.
  • Increase folate demand and depleted body stores.
  • Dialysis induced blood and iron loss.
  • Vitamin B12 deficiency - malnourished.
  • Systemic infection/inflammatory diseases.
  • Severe hyperparathyroidism leading to myelofibrosis.
  • Aluminium overload
  • Haemoglobinopathies e.g. α-thalassemia
  • Hypothyroidism
  • Drug-induced anaemia

Drugs involved in the management of renal anaemia are

  • Erythropoiesis-stimulating agent (ESA)
  • Iron

Blood transfusion should be reserved for patients who are symptomatic and require rapid correction of anaemia to minimize the risk of allosensitization.



Iron Therapy

Iron deficiency can be treated with either oral (for non-HD CKD patients) or intravenous iron.

  • The KDIGO 2012 guidelines recommend iron therapy in both non-HD and HD patients if TSAT is ≤30% and ferritin levels are ≤500 ng/ml.
  • The KDOQI 2006 guidelines recommend iron therapy if TSAT is ≤20% (non-HD and HD patients) and ferritin levels are ≤100 ng/ml in non-HD patients and ≤200 ng/ml in HD patients.

These criteria are important when using ESAs.

  • ESAs help maintain Hb levels and reduce the need for blood transfusions, but they are ineffective if iron stores are low. Hence, evaluate iron status (TSAT and ferritin) at least every 3 months during ESA therapy.
  • Also, intravenous iron has been shown to improve Hb levels and reduce ESA requirements.

For adult patients who undergo dialysis, an empiric cumulative or total dose of 1000 mg is usually given, and equations are rarely used.



Erythropoiesis-Stimulating Agent (ESA)

ESAs are clinically equivalent.

  • The darbepoetin (given weekly) half-life is 3-fold longer than epoetin alfa (given 3 times a week).
  • ESAs are temperature sensitive. All should be kept between 2-8°C. Once cold chain is broken, the ESAs should be used within the period as stated by individual product.

Prior to starting ESA therapy, the patient's blood pressure has to be controlled and iron level must be corrected to target.

  • Initiate when Hb <10 g/dL; Maximal increase in Hb is about 1 g/dL every 2-4 weeks. Titrate dose up or down by 25% based on Hb levels; do not increase the dose more frequently than once every 4 weeks.
  • ESA must not be used to maintain Hb >11.5 g/dL.
  • ESA must not be used to intentionally raise Hb above 13 g/dL.

Studies suggest that treatment with ESAs to high Hgb concentrations (greater than 13 g/dL) increases cardiovascular events.

Contraindications: Uncontrolled hypertension, pure red cell aplasia (PRCA) secondary to any erythropoietin protein drugs and known hypersensitivity to any component of ESA



Red Cell Transfusion

When managing chronic anaemia, the benefits of red cell transfusions may outweigh the risks in patients in whom
  • ESA therapy is ineffective (e.g., hemoglobinopathies, bone marrow failure, ESA resistance).
  • The risks of ESA therapy may outweigh its benefits (e.g., previous or current malignancy, previous stroke).



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