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  • Quality of Evidence
  • Diagnosis and Evaluation
  • Iron Usage
  • Using ESAs
  • ESA Usage (2)
  • Transfusions

KDIGO Guidelines Aug 1 2012

Implications of the quality of evidence and strength of recommendations
Strength of Recommendation
Grade Implications for management

Level 1

“We recommend…”

Most should receive the recommended course of action.

Level 2

"We suggest…”

Different courses of action may be appropriate depending on circumstances.

Not Graded Typically used to provide guidance based on common sense or where the topic does not allow adequate application of evidence.
Levels of Evidence
Grade Quality of evidence Meaning
A High We are confident that the true effect lies close to that of the estimate of the effect.
B Moderate The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
C Low The true effect may be substantially different from the estimate of the effect.
D Very Low The estimate of effect is very uncertain, and often will be far from the truth.

Chapter 1: Diagnosis and evaluation of anemia in CKD

Testing for Anemia
When clinically indicated and:
CKD 3 CKD 4-5ND CKD 5HD and 5PD

CKD patients without anemia

At least annually

(Section 1.1.1)

At least twice per year

(Section 1.1.1)

At least every 3 months

(Section 1.1.1)         

CKD patients with anemia but not treated with an ESA

At least every 3 months
(Section 1.1.2)

(Section 1.1.2)

At least monthly in 5HD and at least every 3 months in
5PD

(Section 1.1.2)
Diagnosis and investigation of anemia
When clinically indicated and:
Adults and children >15 years old

Hemoglobin concentration

(g/l)

Male

<130 (Section 1.2.1)

Female <120 (Section 1.2.1)
Children
0.5-5 years old <110 (Section 1.2.2)
5-12 years old <115 (Section 1.2.2)
12-15 years old <120 (Section 1.2.2)

Investigation of anemia

In patients with CKD and anemia ( regardless of age and CKD stage), include the following tests in initial evaluation of anemia:

  • Complete blood count ( CBC) including Hb concentration, red cell indices, WBC count and differential and platelet count (Section 1.3)

Chapter 2: Use of iron to treat anemia in CKD

Treatment with iron agents
Patient Type Clinical Parameters Treatment Plan
Adult CKD patients with anemia not on iron or ESA therapy - If an increase in HB concentration without ESA treatment is desired* and -TSAT is ≤30% and ferritin is ≤500µg/l
(Section 2.1.2)
We suggest a trial of IV iron or in CKD ND patients alternatively a 1-3 month trial of oral iron therapy (2C)
(Section 2.1.2)
Adult CKD patients on ESA therapy, not receiving iron supplementation - If an increase in HB concentration** or a decrease in ESA dose is desired*** and -TSAT is ≤30% and ferritin is ≤500µg/l
(Section 2.1.3)
We suggest a trial of IV iron or in CKD ND patients alternatively a 1-3 month trial of oral iron therapy (2C)
(Section 2.1.3)
All pediatric CKD patients with anemia not on iron or ESA therapy When TSAT is ≤20% and ferritin is ≤100µg/l
(Section 2.1.6)
We recommend oral iron or IV iron in CKD HD patients (1D)
(Section 2.1.6)
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
  • Cost

(Section 2.1.4)
In all CKD patients:
Guide subsequent iron administration based on:
  • Hb responses to recent iron therapy
  • Ongoing blood losses
  • Iron status tests (TSAT and ferritin)
  • Hb concentrations
  • ESA responsiveness
  • ESA dose in ESA treated patients
  • Trends in each parameter
  • The patient's clinical status

(Section 2.1.5)

* Based on patient symptoms and overall clinical goals, including avoidance of transfusion, improvement in anemia-related symptoms, and after exclusion of active infection

** Consistent with recommendation #3.4.2 and 3.4.3

*** 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.

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.

(Section 2.2.1)

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 my become depleted.

(Section 2.2.2)

Cautions regarding iron therapy
Iron therapy given Clinical Parameters
When the initial dose of IV dextran is administered

We recommend 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 (1B)

( page 26)
When the initial dose of IV non-dextran iron is administered

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 (2C)

(Section 2.3)
Iron during infection:

Avoid administering IV iron to patients with active systemic infections.

(Section 2.4)

Chapter 3: Use of ESAs and other agents to treat anemia in CKD

ESA Initiation

Prior to initiation of ESA therapy:

Address all correctable causes of anemia ( including iron deficiency and inflammatory states) (not graded)

(Section 3.1)
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). (1B)

(Section 3.2)
We recommend using ESA therapy with great caution, if at all, in:
  • CKD patients with active malignancy, in particular when cure is the anticipated outcome (1B)
(Section 3.3)
  • CKD patients with a history of stroke ( 1B)
(Section 3.3)
  • CKD patients with a history of malignancy (2C)
(Section 3.3)
CKD patient group Specific recommendation on ESA intiation
Adult CKD ND patient with Hb ≥100 g/l

We suggest that ESA therapy not be initiated (2D)

(Section 3.4.1)
Adult CKD ND patient with Hb <100 g/l

We suggest that the decision whether to initiate ESA therapy be individualized based on (2C):

  • The rate of fall of Hb concentration
  • Prior response to iron therapy
  • The risk of needing a transfusion
  •  The risks related to ESA therapy
  • The presence of symptoms attributable to anemia
(Section 3.4.2)
Adult CKD 5D patient

We suggest that ESA therapy be used to avoid having the Hb concentration fall below 90 g/l by starting ESA therapy when the hemoglobin is between 90-100 g/l (2B)

(Section 3.4.3)
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. (2D)

(Section 3.4.5)

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 100 g/l. ( not graded)

(Section 3.4.4)
ESA Maintenance Therapy
General recommendations

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. (2C)

(Section 3.5.1)

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. (not graded)

(Section 3.5.2)
Adult patients

In all adult patients, we recommend that ESAs not be used to intentionally increase the Hb concentration above 13 g/dl (130 g/l). (1A)

(Section 3.6)
Pediatric patients

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). (2D)

(Section 3.7)
ESA Dosing
Initial dose

We recommend determining the initial ESA dose using the patient’s Hb concentration, body weight, and clinical
circumstances. (1D)

(Section 3.8.1)
Dose adjustments

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. (1B)

(Section 3.8.2)
Adjusting Hb downwards

We suggest decreasing ESA dose in preference to withholding ESA when a downward adjustment of Hb concentration is needed. (2C)

(Section 3.8.3)
Re-evaluating dose

Re-evaluate ESA dose if (Not Graded):

  • The patient suffers an ESA-related adverse event
  • The patient has an acute or progressive illness that may cause ESA hyporesponsiveness
(Section 3.8.4)
ESA Administration
Patient TypeRoute of administration
CKD 5D patients and those on hemofiltration or hemodiafiltration therapy

We suggest either intravenous or subcutaneous administration of ESA. (2C)

(Section 3.9.1)
CKD ND patients

We suggest subcutaneous administration of ESA. (2C)

(Section 3.9.2)
CKD 5PD patients

We suggest subcutaneous administration of ESA. (2C)

(Section 3.9.2)
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. (2C)

(Section 3.10)
Type of ESA

We recommend choosing an ESA based on the balance of pharmacodynamics, safety information, clinical outcome data, costs, and availability. (1D)

(Section 3.11.1)

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. (2D)

(Section 3.11.2)

Chapter 1: Diagnosis and evaluation of anemia in CKD

Testing for Anemia
When clinically indicated and:
CKD 3 CKD 4-5ND CKD 5HD and 5PD

CKD patients without anemia

At least annually

(Section 1.1.1)

At least twice per year

(Section 1.1.1)

At least every 3 months

(Section 1.1.1)         

CKD patients with anemia but not treated with an ESA

At least every 3 months
(Section 1.1.2)

(Section 1.1.2)

At least monthly in 5HD and at least every 3 months in
5PD

(Section 1.1.2)
Diagnosis and investigation of anemia
When clinically indicated and:
Adults and children >15 years old

Hemoglobin concentration

(g/l)

Male

<130 (Section 1.2.1)

Female <120 (Section 1.2.1)
Children
0.5-5 years old <110 (Section 1.2.2)
5-12 years old <115 (Section 1.2.2)
12-15 years old <120 (Section 1.2.2)

Investigation of anemia

In patients with CKD and anemia ( regardless of age and CKD stage), include the following tests in initial evaluation of anemia:

  • Complete blood count ( CBC) including Hb concentration, red cell indices, WBC count and differential and platelet count (Section 1.3)

Chapter 4: Transfusions

Red cell transfusion to treat anemia in CKD
  Recommendation
In Chronic anemia patients
General recommendation

We recommend avoiding, when possible, red cell transfusions to minimize the general risks related to their use. (1B)

(Section 4.1.1)
Eligible for organ transplantation

We specifically recommend avoiding, when possible, red cell transfusions to minimize the risk of allosensitization. (1C)

(Section 4.1.2)
When ESA therapy is ineffective

We suggest the benefits of red cell transfusions may outweigh the risks in these patients (e.g. hemoglobinopathies, bone marrow failure, ESA resistance). (2C)

(Section 4.1.3)
When ESA therapy risks outweigh those of transfusion

We suggest the benefits of red cell transfusions may outweigh the risks in these patients (e.g. previous or current malignancy, previous stroke). (2C)

(Section 4.1.3)
Deciding to transfuse

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. (2C)

(Section 4.1.4)
For urgent treatment of anemia:
Rapid correction to stabilize the patient’s condition

We suggest patients are transfused when the benefits of red cell transfusions outweigh the risks (e.g. acute hemorrhage, unstable coronary artery disease). (2C)

(Section 4.2)
When rapid pre-operative Hb correction is required

We suggest patients are transfused when the benefits of red cell transfusions outweigh the risks. (2C)

(Section 4.2)