Last updated January 5, 2022

Anemia In Chronic Kidney Disease

Recommendation Statements

Diagnosis and evaluation of anemia in CKD

TESTING FOR ANEMIA

Frequency of testing for anemia
For CKD patients without anemia, measure Hb concentration when clinically indicated and:
  • at least annually in patients with CKD 3
  • at least twice per year in patients with CKD 4–5ND
  • at least every 3 months in patients with CKD 5HD and CKD 5PD
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For CKD patients with anemia not being treated with an ESA, measure Hb concentration when clinically indicated and:
  • at least every 3 months in patients with CKD 3–5ND and CKD 5PD
  • at least monthly in patients with CKD 5HD
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Diagnosis of anemia
Diagnose anemia in adults and children >15 years with CKD when the Hb concentration is <13.0 g/dl (<130 g/l) in males and <12.0 g/dl (<120 g/l) in females. (, )
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Diagnose anemia in children with CKD if Hb concentration is <11.0 g/dl (<110 g/l) in children 0.5–5 years, <11.5 g/dl (115 g/l) in children 5–12 years, and <12.0 g/dl (120 g/l) in children 12–15 years. (, )
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Investigation of anemia
In patients with CKD and anemia (regardless of age and CKD stage), include the following tests in initial evaluation of the anemia:
  • Complete blood count (CBC), which should include Hb concentration, red cell indices, white blood cell count and differential, and platelet count
  • Absolute reticulocyte count
  • Serum ferritin level
  • Serum transferrin saturation (TSAT)
  • Serum vitamin B12 and folate levels
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Use of iron to treat anemia in CKD

TREATMENT WITH IRON AGENTS

When prescribing iron therapy, balance the potential benefits of avoiding or minimizing blood transfusions, ESA therapy, and anemia-related symptoms against the risks of harm in individual patients (e.g., anaphylactoid and other acute reactions, unknown long-term risks). (, )
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For adult CKD patients with anemia not on iron or ESA therapy we suggest a trial of IV iron (or in CKD ND patients alternatively a 1–3 month trial of oral iron therapy) if:
  • an increase in Hb concentration without starting ESA treatment is desired* and
  • TSAT is ≤30% and ferritin is ≤500 ng/ml (≤500 mg/l) 
(Conditional (weak)  “We suggest”, Low)
*Based on patient symptoms and overall clinical goals, including avoidance of transfusion, improvement in anemia-related symptoms, and after exclusion of active infection.
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For adult CKD patients on ESA therapy who are not receiving iron supplementation, we suggest a trial of IV iron (or in CKD ND patients alternatively a 1–3 month trial of oral iron therapy) if:
  • an increase in Hb concentration or a decrease in ESA dose is desired** and
  • TSAT is ≤30% and ferritin is ≤500 ng/ml (≤500 mg/l)
(Conditional (weak)  “We suggest”, Low)
**Based on patient symptoms and overall clinical goals including avoidance of transfusion and improvement in anemia-related symptoms, and after exclusion of active infection and other causes of ESA hyporesponsiveness.
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For CKD ND patients who require iron supplementation, select the route of iron administration based on the severity of iron deficiency, availability of venous access, response to prior oral iron therapy, side effects with prior oral or IV iron therapy, patient compliance, and cost. (, )
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Guide subsequent iron administration in CKD patients based on Hb responses to recent iron therapy, as well as ongoing blood losses, iron status tests (TSAT and ferritin), Hb concentration, ESA responsiveness and ESA dose in ESA treated patients, trends in each parameter, and the patient’s clinical status. (, )
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For all pediatric CKD patients with anemia not on iron or ESA therapy, we recommend oral iron (or IV iron in CKD HD patients) administration when TSAT is >20% and ferritin is >100 ng/ml (>100 lg/l). (Strong  “We recommend”, Very low)
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For all pediatric CKD patients on ESA therapy who are not receiving iron supplementation, we recommend oral iron (or IV iron in CKD HD patients) administration to maintain TSAT >20% and ferritin >100 ng/ml (>100 lg/ l). (Strong  “We recommend”, Very low)
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IRON STATUS EVALUATION

Evaluate iron status (TSAT and ferritin) at least every 3 months during ESA therapy, including the decision to start or continue iron therapy. (Not Graded) (, )
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Test iron status (TSAT and ferritin) more frequently when initiating or increasing ESA dose, when there is blood loss, when monitoring response after a course of IV iron, and in other circumstances where iron stores may become depleted. (, )
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CAUTIONS REGARDING IRON THERAPY

When the initial dose of IV iron dextran is administered, 
we recommend and when the initial dose of IV nondextran iron is administered and
(Strong  “We recommend”, Moderate)
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we suggest that patients be monitored for 60 minutes after the infusion, and that resuscitative facilities (including medications) and personnel trained to evaluate and treat serious adverse reactions be available.
(Conditional (weak)  “We suggest”, Low)
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Iron during infection
Avoid administering IV iron to patients with active systemic infections. (-)
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Use of erythropoiesis-stimulating agents (ESAs) and other agents to treat anemia in CKD

ESA INITIATION

Address all correctable causes of anemia (including iron deficiency and inflammatory states) prior to initiation of ESA therapy.
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In initiating and maintaining ESA therapy, we recommend balancing the potential benefits of reducing blood transfusions and anemia-related symptoms against the risks of harm in individual patients (e.g., stroke, vascular access loss, hypertension). (Strong  “We recommend”, Moderate)
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We recommend using ESA therapy with great caution, if at all,
CKD patients with active malignancy—in particular when cure is the anticipated outcome—,
(Strong  “We recommend”, Moderate)
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a history of stroke,
(Strong  “We recommend”, Moderate)
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a history of malignancy.
(Conditional (weak)  “We suggest”, Low)
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  • For adult CKD ND patients with Hb concentration ≥10.0 g/dl (≥100 g/l), we suggest that ESA therapy not be initiated.
(Conditional (weak)  “We suggest”, Very low)
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  • For adult CKD ND patients with Hb concentration <10.0 g/dl (<100 g/l) we suggest that the decision whether to initiate ESA therapy be individualized based on the rate of fall of Hb concentration, prior response to iron therapy, the risk of needing a transfusion, the risks related to ESA therapy and the presence of symptoms attributable to anemia.
(Conditional (weak)  “We suggest”, Low)
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  • For adult CKD 5D patients, we suggest that ESA therapy be used to avoid having the Hb concentration fall below 9.0 g/dl (90 g/l) by starting ESA therapy when the hemoglobin is between 9.0–10.0 g/dl (90–100 g/l).
(Conditional (weak)  “We suggest”, Moderate)
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  • Individualization of therapy is reasonable as some patients may have improvements in quality of life at higher Hb concentration and ESA therapy may be started above 10.0 g/dl (100 g/l).
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  • For all pediatric CKD patients, we suggest that the selection of Hb concentration at which ESA therapy is initiated in the individual patient includes consideration of potential benefits (e.g., improvement in quality of life, school attendance/performance, and avoidance of transfusion) and potential harms.
(Conditional (weak)  “We suggest”, Very low)
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ESA MAINTENANCE THERAPY

In general, we suggest that ESAs not be used to maintain Hb concentration above 11.5 g/dl (115 g/l) in adult patients with CKD. (Conditional (weak)  “We suggest”, Low)
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Individualization of therapy will be necessary as some patients may have improvements in quality of life at Hb concentration above 11.5 g/dl (115 g/l) and will be prepared to accept the risks. (, )
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In all adult patients, we recommend that ESAs not be used to intentionally increase the Hb concentration above 13 g/dl (130 g/l). (Strong  “We recommend”, High)
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In all pediatric CKD patients receiving ESA therapy, we suggest that the selected Hb concentration be in the range of 11.0 to 12.0 g/dl (110 to 120 g/l). (Conditional (weak)  “We suggest”, Very low)
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ESA DOSING

We recommend determining the initial ESA dose using the patient’s Hb concentration, body weight, and clinical circumstances. (Strong  “We recommend”, Very low)
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We recommend that ESA dose adjustments be made based on the patient’s Hb concentration, rate of change in Hb concentration, current ESA dose and clinical circumstances. (Strong  “We recommend”, Moderate)
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We suggest decreasing ESA dose in preference to withholding ESA when a downward adjustment of Hb concentration is needed. (Conditional (weak)  “We suggest”, Low)
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Re-evaluate ESA dose if:
  • The patient suffers an ESA-related adverse event
  • The patient has an acute or progressive illness that may cause ESA hyporesponsiveness
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ESA ADMINISTRATION

For CKD 5HD patients and those on hemofiltration or hemodiafiltration therapy, we suggest either intravenous or subcutaneous administration of ESA. (Conditional (weak)  “We suggest”, Low)
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For CKD ND and CKD 5PD patients, we suggest subcutaneous administration of ESA. (Conditional (weak)  “We suggest”, Low)
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Frequency of administration
We suggest determining the frequency of ESA administration based on CKD stage, treatment setting, efficacy considerations, patient tolerance and preference, and type of ESA. (Conditional (weak)  “We suggest”, Low)
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TYPE OF ESA

We recommend choosing an ESA based on the balance of pharmacodynamics, safety information, clinical outcome data, costs, and availability. (Strong  “We recommend”, Very low)
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We suggest using only ESAs that have been approved by an independent regulatory agency. Specifically for ‘copy’ versions of ESAs, true biosimilar products should be used. (Conditional (weak)  “We suggest”, Very low)
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EVALUATING AND CORRECTING PERSISTENT FAILURE TO REACH OR MAINTAIN INTENDED HEMOGLOBIN CONCENTRATION

During the initiation phase of ESA therapy, measure Hb concentration at least monthly. (, )
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For CKD ND patients, during the maintenance phase of ESA therapy measure Hb concentration at least every 3 months. (, )
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For CKD 5D patients, during the maintenance phase of ESA therapy measure Hb concentration at least monthly. (, )
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Initial ESA hyporesponsiveness
Classify patients as having ESA hyporesponsiveness if they have no increase in Hb concentration from baseline after the first month of ESA treatment on appropriate weight-based dosing. (, )
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In patients with ESA hyporesponsiveness, we suggest avoiding repeated escalations in ESA dose beyond double the initial weight-based dose. (Conditional (weak)  “We suggest”, Very low)
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Subsequent ESA hyporesponsiveness
Classify patients as having acquired ESA hyporesponsiveness if after treatment with stable doses of ESA, they require 2 increases in ESA doses up to 50% beyond the dose at which they had been stable in an effort to maintain a stable Hb concentration. (, )
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In patients with acquired ESA hyporesponsiveness, we suggest avoiding repeated escalations in ESA dose beyond double the dose at which they had been stable. (Conditional (weak)  “We suggest”, Very low)
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Management of poor ESA responsiveness
Evaluate patients with either initial or acquired ESA hyporesponsiveness and treat for specific causes of poor ESA response. (, )
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For patients who remain hyporesponsive despite correcting treatable causes, we suggest individualization of therapy, accounting for relative risks and benefits of:
  • decline in Hb concentration K continuing ESA, if needed to maintain Hb concentration, with due consideration of the doses required, and
  • blood transfusions
(Conditional (weak)  “We suggest”, Very low)
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ADJUVANT THERAPIES

We recommend not using androgens as an adjuvant to ESA treatment. (Strong  “We recommend”, Moderate)
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We suggest not using adjuvants to ESA treatment including vitamin C, vitamin D, vitamin E, folic acid, L-carnitine, and pentoxifylline. (Conditional (weak)  “We suggest”, Very low)
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EVALUATION FOR PURE RED CELL APLASIA (PRCA)

Investigate for possible antibody-mediated PRCA when a patient receiving ESA therapy for more than 8 weeks develops the following:
  • Sudden rapid decrease in Hb concentration at the rate of 0.5 to 1.0 g/dl (5 to 10 g/l) per week OR requirement of transfusions at the rate of approximately 1 to 2 per week, AND
  • Normal platelet and white cell counts, AND
  • Absolute reticulocyte count less than 10,000/ml
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We recommend that ESA therapy be stopped in patients who develop antibody-mediated PRCA. (Strong  “We recommend”, High)
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We recommend peginesatide be used to treat patients with antibody-mediated PRCA. (Strong  “We recommend”, Moderate)
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Red cell transfusion to treat anemia in CKD

USE OF RED CELL TRANSFUSION IN CHRONIC ANEMIA

When managing chronic anemia, we recommend avoiding, when possible, red cell transfusions to minimize the general risks related to their use. (Strong  “We recommend”, Moderate)
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In patients eligible for organ transplantation, we specifically recommend avoiding, when possible, red cell transfusions to minimize the risk of allosensitization. (Strong  “We recommend”, Low)
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When managing chronic anemia, we suggest that 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)
(Conditional (weak)  “We suggest”, Low)
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We suggest that the decision to transfuse a CKD patient with non-acute anemia should not be based on any arbitrary Hb threshold, but should be determined by the occurrence of symptoms caused by anemia. (Conditional (weak)  “We suggest”, Low)
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URGENT TREATMENT OF ANEMIA

In certain acute clinical situations, we suggest patients are transfused when the benefits of red cell transfusions outweigh the risks; these include: 
  • hen rapid correction of anemia is required to stabilize the patient’s condition (e.g., acute hemorrhage, unstable coronary artery disease)
  • When rapid pre-operative Hb correction is required.
(Conditional (weak)  “We suggest”, Low)
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Recommendation Grading

Overview

Title

Anemia in Chronic Kidney Disease

Authoring Organization

Publication Month/Year

August 1, 2012

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory, Hospital, Operating and recovery room, Outpatient

Intended Users

Dietician nutritionist

Scope

Assessment and screening, Diagnosis, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D000740 - Anemia, D018798 - Anemia, Iron-Deficiency

Keywords

erythropoiesis-stimulating agents, anemia in CKD, blood transfusions