What is the management of anemia in Chronic Kidney Disease (CKD)?

Management of Anemia in Chronic Kidney Disease

The management of anemia in CKD requires a structured approach focusing on iron therapy first, followed by erythropoiesis-stimulating agents (ESAs) when necessary, with careful monitoring to balance efficacy against potential cardiovascular risks. 1, 2

Pathophysiology and Diagnosis

• Anemia in CKD results from multiple factors including reduced erythropoietin production, poor bone marrow responsiveness, shortened red blood cell survival, direct bone marrow suppression, and iron dysregulation 3
• Diagnosis requires measurement of hemoglobin, transferrin saturation (TSAT), and serum ferritin in all CKD patients 2
• Absolute iron deficiency is defined as TSAT <20% and ferritin <100 mg/L in non-dialysis patients or <200 mg/L in hemodialysis patients 3
• Functional iron deficiency is defined as TSAT <20% with ferritin >100 mg/L in non-dialysis patients or >200 mg/L in hemodialysis patients 3
• Traditional parameters (ferritin, TSAT) have limitations in predicting response to therapy; newer parameters like reticulocyte hemoglobin content may provide more accurate assessment 3, 2

Iron Therapy - First Line Treatment

• IV iron should be the first-line treatment for anemia in advanced CKD patients, as it can significantly improve hemoglobin levels without ESA therapy 1
• A trial of IV iron is recommended when TSAT is ≤30% and ferritin is ≤500 ng/mL 1
• For non-dialysis CKD patients with milder anemia, start with oral iron if TSAT <20% and ferritin <100 mg/L 2
• For hemodialysis patients, target TSAT ≥20% and ferritin ≥200 mg/L before considering ESA therapy 2
• IV iron administration options include iron sucrose (maximum 200-500 mg per infusion) or ferric carboxymaltose (up to 1000 mg per week) 2
• Avoid excessive iron supplementation; withhold IV iron if ferritin >500 ng/mL and/or TSAT >30% 1

ESA Therapy - Second Line Treatment

• Consider ESA therapy if hemoglobin fails to improve adequately after optimizing iron stores 1, 4
• Before starting ESA, ensure all correctable causes of anemia have been addressed 1
• ESAs indicated for treatment of anemia due to CKD, including patients on dialysis and not on dialysis 4, 5, 4
• Use the lowest ESA dose sufficient to reduce the need for red blood cell transfusions 4
• In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when ESAs were used to target hemoglobin >11 g/dL 4
• No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase cardiovascular risks 4
• Monitor hemoglobin at least weekly after initiating therapy or dose adjustments until stable, then monthly 4

Management of ESA Hyporesponse

• ESA hyporesponse is defined as failure to achieve hemoglobin of 11 g/dL with epoetin >300 IU/kg/week or darbepoetin alpha >1.5 μg/kg/week 6
• Common causes include iron deficiency, inflammation, secondary hyperparathyroidism, inadequate dialysis, malnutrition, and medication effects 7
• Management involves treating infections, ensuring adequate nutrition, optimizing iron status and dialysis adequacy 7
• Consider HIF-prolyl hydroxylase inhibitors (HIF-PHIs) for ESA hyporesponsive patients, as they can increase hemoglobin and reduce hepcidin regardless of inflammation or iron status 7

Blood Transfusions

• Blood transfusions should generally be avoided when possible in CKD patients to minimize risks of allosensitization 1
• Reserve transfusions for situations where the patient becomes symptomatic, ESA therapy is ineffective or contraindicated, or rapid correction of anemia is required 1
• Avoid reflexive blood transfusions based solely on hemoglobin level without considering patient's clinical status 1

Monitoring Recommendations

• For CKD patients with anemia not on ESA therapy, measure hemoglobin at least every 3 months 1
• For patients on ESA therapy, monitor hemoglobin weekly until stable, then at least monthly 4
• Monitor iron status before and after iron therapy to guide subsequent treatment decisions 1, 2
• When adjusting ESA therapy, consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability 4
• If hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the ESA dose by 25% or more 4

Emerging Therapies

• HIF-PHIs represent a novel class of agents for treating renal anemia that may alter iron metabolism differently than ESAs 2
• Special consideration needed for specific patient populations (diabetic nephropathy, polycystic kidney disease) when using HIF-PHIs 2
• Further research is needed to determine optimal iron management strategies for HIF-PHI therapy 3