Applied Evidence

Anemia and chronic kidney disease: What’s the connection?

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Aim for complete anemia resolution? That’s controversial

Treatment of CKD anemia with ESAs is widely practiced, but controversy over whether it is beneficial to aim for complete resolution of anemia is ongoing. The CREATE (Cardiovascular Risk Reduction by Early Anemia Treatment) and CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trials published in 2006 failed to resolve the issue.12,13

In the CREATE trial, patients targeted to achieve normal hemoglobin levels did no better in avoiding cardiovascular events than patients targeted for lower levels. The CHOIR trial was stopped early because of an increased trend toward death and hospitalization for congestive heart failure in the group with therapy targeted to achieve normal hemoglobin levels.

The recently published TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study of patients with type 2 diabetes and CKD showed no reduction in all-cause mortality, cardiovascular morbidity, or ESRD in patients receiving Aranesp targeted to achieve a hemoglobin level of approximately 13 g/dL, compared with placebo.14 The study did demonstrate, however, that patients receiving Aranesp were about twice as likely to have a stroke than the placebo subjects (101 vs 53)—which might lead clinicians to ponder whether the gains, if any, were worth the risk.

Revised labeling. Late last year, the US Food and Drug Administration approved a label change for Procrit and Aranesp, warning that patients with renal failure “experienced greater risks for death and serious cardiovascular events when administered ESAs to target higher vs lower hemoglobin levels” and advising physicians to “individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.”10,11 The 2007 NKF KDOQI guidelines suggest maintaining a hemoglobin level between 11 and 12 g/dL and have not incorporated the results of the TREAT trial.

Some patients don’t respond to ESAs

Inadequate response to ESAs is most commonly caused by underdosing or inadequate iron stores. NKF KDOQI guidelines recommend checking TSAT and ferritin prior to initiating therapy and monitoring these levels every 3 months.3 True nonresponders are individuals with good iron stores who are unable to achieve target hemoglobin within 4 to 6 months despite receiving subcutaneous epoetin 300 IU/kg per week. Inadequate response to ESAs can be caused by ongoing occult blood loss, infection, inflammation, nutritional deficiencies, hemolysis, hemoglobinemias, aluminum toxicity, anti-EPO antibody, hyperparathyroidism, multiple myeloma, and bone marrow dysfunction.10,11 If patients do not respond to ESA therapy, the NKF KDOQI guidelines recommend referral to a nephrologist or hematologist.3

How did Mary fare?
Mary did well taking oral iron supplementation. Once her iron deficiency was corrected, you were able to begin treating her anemia. After appropriate titration of her ESA, she was able to maintain a hemoglobin level between 11 and 12 g/dL 4 months into therapy. On a follow-up visit, she had no side effects from the medication and reported an increase in her energy level.

Jonathan Taliercio, DO, Cleveland Clinic, Department of Nephrology and Hypertension, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]


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