Table 1.
Summary of current clinical guidelines to treat anemia in adult patients with nondialysis-dependent CKD
| Guideline | Diagnosis of Anemia | ESA Use | Iron Use | Hb Target | TSAT/Ferritin Target | Phosphorus Target | Adjuvants |
| KDIGO (1,83) | Hb<130 g/L in men >15 yr; Hb<120 g/L in women >15 yr | Initiate ESA therapy in those with Hb<100 g/L after all other correctable causes of anemia have been addressed and symptoms of anemia are present and for avoiding transfusions; therapy should be individualized for each patienta | 1- to 3-mo trial of oral iron or iv ironb if TSAT is <30% and ferritin is <500 μg/L or ESA therapy is to be avoided or decreased (if already on ESA therapy) | Hb≤115 g/L in adults on ESA therapy but should be on the basis of individual patients | TSAT>30%/ferritin >500 μg/L | CKD stages 3–5: Maintain serum phosphorus within the normal range | Not recommended: androgens, vitamin C, vitamin D, vitamin E, folic acid, l-carnitine, and pentoxifylline |
| KDOQI (2,84) | Hb<135 g/L in adult men; Hb<120 g/L in adult women | Initial ESA dose and ESA dose adjustments determined by the patient’s Hb level, target Hb level, rate of increase in Hb level, and clinical circumstancesc | Oral or iv iron administered to maintain ferritin >100 μg/L and TSAT>20% during ESA treatmentd | Hb>110 g/L; ESA-treated patients should not be routinely maintained at Hb≥130 g/L | TSAT≥20%/ferritin >100 and <500 μg/L | Stages 3 and 4 CKD: ≥2.76 and <4.61 mg/dl; stage 5 CKD: >3.50 and <5.51 mg/dl | Not routinely recommended: l-carnitine and ascorbate; not recommended: androgens |
| Canadian Society of Nephrology (3–6,85) | Hb<135 g/L in men ≥18 yr; Hb<120 g/L in women ≥18 yr | Initiate ESA therapy when iron stores have been corrected, other reversible causes of anemia have been treated, and Hb level is sustained at <100 g/L in patients not receiving ESA therapye; for patients receiving ESA therapy, target Hb is 110 g/L | Oral or iv iron to maintain target concentrations of TSAT and ferritinf; iron is not recommended for patients without evidence of classic iron deficiency whose Hb is >110 g/L | Hb<110 g/L (acceptable Hb range =100–120 g/L) | TSAT>20%/ferritin >100 μg/L; iron should be considered if patient is below target Hb or requires high ESA doses and has ferritin >800 μg/L and TSAT<25% | Does not recommend monitoring phosphorus for stage 3 CKD; stages 4 and 5 CKD: Maintain within normal range | Not recommended: androgens; insufficient evidence to recommend: l-carnitine, vitamin C, ultrapure dialysis, pentoxifylline, statins, vitamin B6, and quotidian dialysis |
| NICE (7) | Hb<110 g/L or development of symptoms attributable to anemia (tiredness, shortness of breath, lethargy, and palpitations) | ESA therapy should not be initiated in the presence of absolute iron deficiency without also managing the iron deficiency; ESAs not recommended in the presence of comorbidities or a prognosis that is likely to negate the benefits of correcting the anemiag | Oral or iv iron to maintain hypochromic RBC, reticulocyte, or TSAT and ferritin targets | 100–120 g/L; rate of Hb increase should be between 10 and 20 g/L per mo in patients on ESA therapyh | Recommend using hypochromic RBC >6% (unless ferritin is >800 μg/L) or reticulocyte count >29 pg (unless ferritin is >800 μg/L); if tests are not available, TSAT>20%/ferritin >100 μg/L; maintain ferritin <800 μg/L in patients on iron therapy | Recommend following British, American, and European treatment guidelines | Not recommended: androgens, vitamin C, folic acid, and carnitine |
| ERBP (8,86) | Hb<135 g/L in adult men ≤70 yr; Hb<132 g/L in adult men >70 yr; Hb<120 g/L in adult women | In low-risk patients or those in whom a clear benefit in quality of life can be foreseen, ESA therapy can be considered at Hb<120 g/L; in high-risk patients, ESA therapy should be initiated at Hb values between 90 and 100 g/Li | Oral or iv iron if TSAT is <20% and ferritin is <100 μg/L or if Hb increases without ESA therapy, TSAT is <25%, and ferritin is <200 μg/L; in patients on ESA therapy in whom increase in Hb or decrease in ESA dose is desired, oral or iv iron may be given when TSAT is <30% and ferritin is <300 μg/L | 100–120 g/L; not >130 g/L for patients receiving ESA therapy; approximately 100 g/L in high-risk patients | TSAT≥20%/ferritin =100 μg/L; should not exceed TSAT>30%/ferritin >500 μg/L | For CKD stages 3–5, maintain within normal range | Not recommended |
ESA, erythropoiesis-stimulating agent; Hb, hemoglobin; TSAT, saturated transferrin; KDIGO, Kidney Disease Improving Global Outcomes; iv, intravenous; KDOQI, Kidney Disease Outcomes Quality Initiative; NICE, National Institute for Health and Care Excellence; RBC, red blood cell; ERBP, European Renal Best Practice.
ESA dosing should be on the basis of the individual patient Hb, body weight, and clinical circumstances and should be adjusted on the basis of Hb, rate of change in Hb, current ESA dose, and clinical circumstances. The choice of ESA should be on the basis of the balance of pharmacodynamics, safety information, clinical outcome data, cost, and availability. Subcutaneous dosing is recommended for administration of ESA therapy to patients with nondialysis CKD. Initiation of ESA therapy should be with great caution, if at all, in patients with active malignancy or a history of stroke.
The route of iron administration should be on the basis of the severity of iron deficiency, the availability of venous access, response to prior oral iron therapy, side effects with prior iron therapy, patient compliance, and cost.
The route of ESA administration should be determined by the CKD stage, treatment setting, efficacy, safety, and class of ESA used in adults. The anticipated frequency and pain of administration and the potential effects on the child and family should also be considered in pediatric patients. Convenience favors subcutaneous administration and less frequent ESA administration in adult patients with nondialysis CKD.
Clinicians should judge the individual patient’s clinical status and ESA responsiveness and base iron treatment decisions on this assessment.
ESAs should be administered subcutaneously on the basis of improved efficacy and convenience.
Oral iron is the preferred first–line therapy in patients with nondialysis CKD. In patients who do not meet serum ferritin or TSAT targets on oral iron or in whom oral iron is not tolerated, iv iron may be used. The medical decision regarding the use of iron therapy should be guided by results of iron status tests together with Hb levels, ESA dose, and patient status.
When ESA has been initiated, the effectiveness of the ESA should be assessed after an agreed on interval. Where appropriate, a mutual decision between the clinician, the patient with anemia and CKD, and the family/caregivers should be made on whether to continue ESA therapy. The patient and clinician should agree to the route of ESA administration taking into account the individual patient’s clinical course, pain of injection, frequency of administration, lifestyle and preferences, efficacy, and cost.
When determining individual Hb targets for patients with anemia and CKD, take into account patient preferences, symptoms, comorbidities, and the required treatment.
The decision on whether and when to begin ESA therapy in patients with nondialysis CKD should be individualized and take into account the rate of fall of Hb, prior response to iron therapy, risk of transfusion, risks related to ESA therapy, and the presence of symptoms attributable to anemia. Hb values should not routinely be allowed to fall to <100 g/L in patients with nondialysis CKD. Therapy with ESAs should not be started if there is a temporary and obvious cause of anemia that is potentially reversible. Risk factors for stroke, a history of malignancy, or the presence of active malignancy should be considered when weighing the risk-to-benefit ratio of ESA therapy.