Achieving higher hemoglobin (Hb) levels using an erythropoiesis-stimulating agent (ESA) prior to dialysis initiation does not improve patient outcomes and may increase the risk of stroke, according to a post hoc analysis of TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy).

In TREAT, 590 patients (14.6% of the original cohort) with type 2 diabetes and chronic kidney disease progressed to dialysis. Roughly half had been randomly assigned to receive darbepoetin and half to receive placebo. At dialysis initiation, Hb levels were 11.3 g/dL in the darbepoetin group and 9.5 g/dL for the placebo group, Finnian R. McCausland, MBBCh, MMSc, of Brigham and Women’s Hospital in Boston, and colleagues reported in the American Journal of Kidney Diseases. After the transition to dialysis, there was no study protocol for anemia treatment. Instead, individual physicians decided treatment, including use of ESAs.

After starting dialysis, 10.4% of darbepoetin patients and 9.6% of placebo patients died, with a 16% excess hazard for the intervention group. Cardiovascular deaths occurred in 5% and 4.5%, respectively, with a 21% excess hazard for the intervention group. Although nonfatal myocardial infarction or heart failure occurred in similar proportions of the 2 groups, stroke occurred in significantly more darbepoetin recipients: 8 vs 1.

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“In the absence of more definitive data, our results suggest that treating clinicians and patients should carefully consider the decision to use ESA-based strategies for mild to moderate anemia management for patients preparing for the initiation of dialysis therapy,” Dr Mc Causland’s team wrote.

“Taken together, the results of several RCTs (including TREAT) and the Mc Causland post hoc analysis help inform important aspects of anemia treatment in NDD-CKD,” Steven Fishbane, MD, Daniel W. Ross, MD, and Susana Hong, MD, from the Division of Nephrology, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, commented in an accompanying editorial. “With currently available erythropoietin analogues, treatment of mild anemia in NDD-CKD is probably not advisable. In contrast, treatment of more severe anemia, for example, hemoglobin level < 10 g/dL, should be considered. The risk and benefit consideration should place a particular emphasis on the amount of symptoms and the desire to avoid blood transfusions.”

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McCausland FR, Claggett B, Burdmann EA, et al. Treatment of anemia with darbepoetin prior to dialysis initiation and clinical outcomes: Analyses from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Am J Kidney Dis. DOI:10.1053/j.ajkd.2018.10.006

Fishbane S, Ross DW, Hong S. Anemia in non–dialysis-dependent CKD: To treat or not to treat? Am J Kidney Dis. DOI:10.1053/j.ajkd.2018.11.006