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Anemia of chronic kidney disease

What's new

The United Kingdom Kidney Association (UKKA) has updated its guidelines for the management of anemia of chronic kidney disease. Iron repletion is required before initiating erythropoiesis-stimulating agents (ESAs) or hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), with IV iron preferred in most hemodialysis patients. Proactive high-dose IV iron is recommended unless ferritin is >700 mcg/L or transferrin saturation is >40%. HIF-PHIs are now recommended for symptomatic anemia (Hb <105 g/L) in non-dialysis and dialysis-dependent CKD after iron repletion, particularly in patients with ESA intolerance or resistance. ESA or HIF-PHI therapy should target a hemoglobin range of 100-120 g/L and may be continued during acute illness unless contraindicated. Red blood cell transfusion should be avoided, particularly in transplant candidates, to reduce the risk of alloimmunization. Notably, this is the first major guideline to formally recommend HIF-PHI use ahead of the forthcoming KDIGO update. .

Background

Overview

Definition
Anemia of CKD is usually normocytic, normochromic, and hypoproliferative, which increases as the kidney disease progresses.
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Pathophysiology
Anemia of CKD is mostly caused by a relative deficiency in EPO (EPO) production. Other causes include inflammation, iron deficiency, and accumulation of uremic toxins.
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Disease course
Decreased production of EPO due to worsening kidney function results in anemia of CKD, which causes clinical manifestations of decreased QoL, cognitive impairment, sleep disturbances, CKD progression, and cardiovascular comorbidities.
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Prognosis and risk of recurrence
Anemia of CKD among diabetics is associated with higher mortality (HR 3.61, 95% CI 2.48-5.26).
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of anemia of chronic kidney disease are prepared by our editorial team based on guidelines from the United Kingdom Kidney Association (UKKA 2025), the Japanese Society of Nephrology (JSN 2019), the British Committee for Standards In Haematology (BCSH 2013), and the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2012).
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Screening and diagnosis

Indications for screening
As per UKKA 2025 guidelines:
Consider measuring hemoglobin level at least annually to screen for anemia in patients with CKD stage 3.
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Consider measuring hemoglobin level at least twice a year to screen for anemia in patients with CKD stages 4-5 not on RRT.
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  • Diagnostic criteria

Diagnostic investigations

Initial evaluation: as per UKKA 2025 guidelines, evaluate all patients with chronic anemia associated with CKD for the cause and possible treatment in case of hemoglobin levels < 110 g/L (< 105 g/L in patients aged < 2 years) or symptoms attributable to anemia, irrespective of the grade of kidney disease or requirement for RRT.
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  • EPO measurement

  • Evaluation for functional iron deficiency

Medical management

Iron therapy, iron deficiency with anemia: as per JSN 2019 guidelines, consider administering iron therapy in patients with CKD and iron deficiency anemia.
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  • Iron therapy (iron deficiency without anemia)

  • Iron therapy (route of administration)

  • Iron therapy (upper limit)

  • Iron therapy (safety)

  • Iron therapy (monitoring)

  • ESAs (initiation)

  • ESAs (choice of agent)

  • ESAs (route of administration)

  • ESAs (dosing)

  • ESAs (treatment targets)

  • ESAs (maintenance)

  • ESAs (monitoring)

  • ESAs (management of ESA-induced pure red cell aplasia)

  • ESAs (management of ESA hyporesponsiveness)

  • Hypoxia-inducible factor prolyl hydroxylase inhibitors (initiation)

  • Hypoxia-inducible factor prolyl hydroxylase inhibitors (dosing)

  • Hypoxia-inducible factor prolyl hydroxylase inhibitors (treatment targets)

  • Hypoxia-inducible factor prolyl hydroxylase inhibitors (maintenance)

  • Hypoxia-inducible factor prolyl hydroxylase inhibitors (safety)

  • Hypoxia-inducible factor prolyl hydroxylase inhibitors (monitoring)

  • Adjuvant therapies

Therapeutic procedures

RBC transfusion: as per UKKA 2025 guidelines, avoid administering RBC transfusions in patients with anemia of CKD, particularly when kidney transplantation is an option, to minimize the risk of allosensitization.
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Specific circumstances

Pregnant patients
As per UKKA 2025 guidelines:
Administer parenteral iron in pregnant and postpartum patients with CKD from the second trimester onwards, if indicated, and if the benefit is judged to outweigh the potential risk for the mother and fetus, following the summary of product characteristics guidance.
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Continue ESA therapy during pregnancy unless there is a major contraindication, such as hypertension or thrombosis risk.
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  • Renal transplant recipients

  • Patients with malignancy