Chronic Kidney Disease–Associated Anaemia

Anaemia is a common complication of Chronic Kidney Disease (CKD) and becomes increasingly prevalent as kidney function declines. It primarily results from reduced production of erythropoietin by the diseased kidneys but may also be aggravated by iron deficiency, chronic inflammation, blood loss, nutritional deficiencies, shortened red blood cell survival, and dialysis-related losses.

CKD-associated anaemia contributes to fatigue, reduced exercise tolerance, impaired quality of life, left ventricular hypertrophy, cardiovascular disease, increased hospitalization, and mortality. Early diagnosis and appropriate treatment with iron supplementation and erythropoiesis-stimulating agents (ESAs) improve clinical outcomes and reduce complications.

Epidemiology

Anaemia affects a substantial proportion of patients with CKD, with prevalence increasing progressively from Stage 3 onwards. More than half of patients with advanced CKD and most patients receiving dialysis develop anaemia. In sub-Saharan Africa, including Tanzania, CKD-associated anaemia is frequently compounded by nutritional deficiencies, chronic infections, and delayed presentation for specialist care.

Risk factors

Common risk factors include:

• Chronic Kidney Disease, particularly Stages 3–5

• Reduced erythropoietin production

• Iron deficiency

• Blood loss from gastrointestinal disease

• Blood loss during haemodialysis

• Chronic inflammation

• Poor nutritional intake

• Folate or vitamin B12 deficiency

• Frequent blood sampling

• Secondary hyperparathyroidism

• Advanced age

Pathophysiology

Healthy kidneys produce erythropoietin, which stimulates red blood cell production in the bone marrow. Progressive loss of kidney function reduces erythropoietin production, leading to decreased erythropoiesis and anaemia.

Iron deficiency commonly coexists because of reduced gastrointestinal absorption, chronic blood loss, repeated haemodialysis, and increased iron utilization following treatment with erythropoiesis-stimulating agents. Chronic inflammation also contributes through increased hepcidin production, reducing iron availability for erythropoiesis.

Clinical presentation

Symptoms depend on the severity of anaemia.

Patients may present with:

• Fatigue

• Generalized weakness

• Reduced exercise tolerance

• Shortness of breath on exertion

• Palpitations

• Dizziness

• Poor concentration

• Loss of appetite

• Symptoms of underlying chronic kidney disease

Clinical signs may include:

• Pallor

• Tachycardia

• Flow murmur

• Features of heart failure in severe anaemia

• Signs of advanced chronic kidney disease

Diagnostic criteria

CKD-associated anaemia should be suspected in patients with chronic kidney disease and reduced haemoglobin after excluding other causes of anaemia.

Patients with CKD Stage 3–5 should undergo evaluation for anaemia.

Erythropoiesis-stimulating agent (ESA) therapy is recommended when:

• Haemoglobin is below 10 g/dL, after appropriate evaluation and correction of reversible causes, particularly iron deficiency.

ESA therapy should be reduced or temporarily interrupted when:

• Haemoglobin reaches or exceeds 11 g/dL, unless otherwise directed by a nephrologist.

Investigations

Patients with CKD Stage 3–5 and anaemia should undergo the following investigations:

Haematological investigations

• Full blood count.

• Peripheral blood smear.

• Reticulocyte count.

Iron studies

• Serum iron.

• Transferrin saturation (TSAT).

• Serum ferritin.

Gastrointestinal evaluation

• Stool for occult blood where gastrointestinal blood loss is suspected.

Additional investigations

• Serum creatinine.

• Estimated glomerular filtration rate (eGFR).

• Vitamin B12 and folate levels where indicated.

• Markers of inflammation where appropriate.

The underlying cause of anaemia should always be identified and corrected whenever possible.

Management

Management aims to:

• Correct anaemia.

• Improve quality of life.

• Reduce cardiovascular complications.

• Minimize the need for blood transfusion.

• Treat reversible causes of anaemia.

Non-pharmacological treatment

General measures include:

• Identify and treat reversible causes of anaemia.

• Optimize nutritional status.

• Treat iron deficiency.

• Manage chronic blood loss where present.

• Monitor haemoglobin regularly.

• Manage underlying chronic kidney disease.

• Refer patients receiving dialysis according to the National Guidelines for Dialysis Services.

Pharmacological treatment

Patients with CKD Stage 3–5 and haemoglobin below 10 g/dL should receive erythropoiesis-stimulating agents after correction of iron deficiency where appropriate.

Recommended treatment:

• Erythropoietin alfa 50–100 units/kg intravenously three times per week as the approximate starting dose.

Dose adjustment should be guided by haemoglobin response.

Reduce or temporarily interrupt treatment when haemoglobin reaches 11 g/dL.

Iron supplementation

Patients with:

• Transferrin saturation (TSAT) below 30%, or

• Serum ferritin below 500 ng/mL

should receive iron supplementation.

Recommended treatment:

• Iron sucrose 100 mg intravenously with each dialysis session for 10 doses.

Intravenous iron is preferred over oral iron in patients receiving haemodialysis and may be administered together with erythropoiesis-stimulating agents.

Blood transfusion should generally be reserved for patients with severe symptomatic anaemia or when rapid correction is required and should be used cautiously to minimize future kidney transplantation sensitization.

Referral

Refer patients to a nephrologist or physician when:

• CKD Stage 3–5 with persistent anaemia.

• Haemoglobin remains below target despite appropriate therapy.

• Severe iron deficiency.

• Suspected alternative causes of anaemia.

• Requirement for dialysis.

• Recurrent blood transfusions are being considered.

• Complications of erythropoiesis-stimulating agent therapy occur.

Patients receiving haemodialysis should be managed according to the National Guidelines for Dialysis Services.

Complications

Potential complications include:

• Reduced quality of life.

• Left ventricular hypertrophy.

• Heart failure.

• Reduced exercise capacity.

• Cognitive impairment.

• Increased hospitalization.

• Increased need for blood transfusion.

• Cardiovascular disease.

• Increased mortality.

Prognosis

The prognosis depends on the severity of anaemia, stage of chronic kidney disease, iron status, cardiovascular comorbidities, and response to treatment. Early diagnosis, correction of iron deficiency, and appropriate use of erythropoiesis-stimulating agents improve symptoms, reduce cardiovascular complications, decrease transfusion requirements, and enhance quality of life.

Prevention

Preventive measures include:

• Early detection and treatment of chronic kidney disease.

• Routine haemoglobin monitoring in patients with CKD Stages 3–5.

• Regular assessment of iron status using transferrin saturation and serum ferritin.

• Prompt treatment of iron deficiency.

• Appropriate use of erythropoiesis-stimulating agents according to clinical guidelines.

• Prevention and treatment of chronic blood loss.

• Nutritional optimization.

• Early referral of patients with advanced CKD to nephrology services.