1. NKF-KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease UPDATE OF HEMOGLOBIN TARGET Am.J.Kidney.Dis. 50 (3):471-530, 2007.

2. KDOQI Anemia Organization  Evidence Review Team  Tufts New England Medical Center  Work Group  9 Adult Nephrologists  2 Pediatric Nephrologists  2 Hematologists  1 Nurse Practitioner  1 Dietician

3. CPR and CPG 2.1: Hb Target Introduction  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.

4. CPR 2.1.1 Considerations  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)

5. CPR 2.1.2 Selection 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)

6. CPG 2.1.3 Hb 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)

7. Rationale: 2.1.2

8. 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

9. 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

10. 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

11. 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 Higher Hb Target 11.7 11.0-11.7 13.0 12.0-14.0 13.0-15.0 13.5 11.0 13.0

12. 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 12.0-14.0 13.0-15.0 13.5 Higher Hb Target

13. 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 Higher Hb Target

14. 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 Higher Hb Target

15. 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