NKF-KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease

UPDATE OF HEMOGLOBIN TARGETAm.J.Kidney.Dis. 50 (3):471-530, 2007.

KDOQI AnemiaOrganization

Evidence Review Team Tufts New England Medical Center

Work Group 9 Adult Nephrologists 2 Pediatric Nephrologists 2 Hematologists 1 Nurse Practitioner 1 Dietician

CPR and CPG 2.1: Hb TargetIntroduction

The Hb target is the intended aim of ESA therapy for the individual CKD patient. In clinical practice, achieved Hb results vary considerably from the Hb target.

CPR 2.1.1Considerations

In the opinion of the work group, selection of the Hb target and selection of the Hb level at which ESA therapy is initiated in the individual patient should include consideration of potential benefits (including improvement in quality of life and avoidance of transfusion) and potential harms (including the risk of life-threatening adverse events). (Clinical Practice RECOMMENDATION)

CPR 2.1.2Selection of the Hb target

In the opinion of the work group, in dialysis and non-dialysis CKD patients receiving ESA therapy, the selected Hb target should generally be in the range of 11.0 to 12.0 g/dL. (Clinical Practice RECOMMENDATION)

CPG 2.1.3Hb targets to avoid

In dialysis and non-dialysis CKD patients receiving ESA therapy, the Hb target should not be above 13.0 g/dL. (Clinical Practice GUIDELINE - MODERATELY STRONG EVIDENCE)

Rationale: 2.1.2

Distinguishing Target Hb from Achieved Hb

Target Hb is the aim of ESA therapy

Achieved Hb is the result of ESA therapy

Achieved Hb results vary considerably from the Hb target

Safety of achieved Hb relative to 11-12 g/dL target Hb or Hb > 11 g/dL threshold is well-established

Rationale: 2.1.2

The Hb target should not be above 13.0 g/dL (Moderately Strong Recommendation)

Evidence from RCTs Considered all trials that compared Hb

target > 13.0 g/dL to lower target All these RCTs tested the hypothesis that

the higher target would prevent adverse cardiovascular events or mortality, or all cause mortality

None showed a benefit on those outcomes

Rationale: 2.1.3

Meta-Analysis

Performed by Evidence Review Team

RCTs with ≥ 6 months follow-up, no restriction on study size

Statistical model: random effects

Separated dialysis from non-dialysis CKD trials

Combined all cardiovascular disease events for analysis of cardiovascular adverse event risk

Relative mortality risk for assignment to higher treatment targets: Non-Dialysis-CKD

Rationale: 2.1.3

Relative Risk: 1.02, 95% CI 0.63-1.61

HigherHb Target

11.711.0-11.7

13.012.0-14.013.0-15.013.0-15.0

13.511.0

13.0

Relative risk of cardiovascular events for assignment to higher targets: Non-dialysis CKD

Rationale: 2.1.3

Relative Risk: 1.24, 95% CI 1.02-1.51

11.7

12.0-14.013.0-15.013.0-15.0

13.0-15.013.5

HigherHb Target

Relative mortality risk for assignment to higher treatment targets: Dialysis CKD

Rationale: 2.1.3

Relative Risk: 1.12, 95% CI 0.91-1.37

14.0

13.0-14.0

13.5-16.0

13.5-14.5

HigherHb Target

Relative risk of cardiovascular events for assignment to higher targets: Dialysis CKD

Relative Risk: 1.14, 95% CI 0.79-1.64

Rationale: 2.1.3

14.0

13.0-14.0

13.5-14.5

HigherHb Target

The Statement: Hb Target should not be above 13 g/dL

Reflects Work Group judgment The possibility to cause harm weighs

more heavily than the potential to improve quality of life and reduce the likelihood of transfusions

Moderately strong, evidence-based, clinical practice guideline

Rationale: 2.1.3