1. ¹Department of Medicine, The Renal Division, Duke University Medical Center, Durham, North Carolina, USA
2. ²Duke Clinical Research Institute, North Carolina, Durham, USA
3. ³Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA
4. ⁴Department of Medicine, University College Galway, Galway, Ireland
5. ⁵Duke Translational Research Institute, Durham, North Carolina, USA
6. ⁶The Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

Correspondence: Lynda A. Szczech, Duke University Medical Center, Division of Nephrology, Department of Medicine, Box 3646, Durham, North Carolina 27710, USA. E-mail: szcze001@mc.duke.edu

Received 26 February 2008; Revised 9 April 2008; Accepted 22 April 2008; Published online 2 July 2008.

Abstract

Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-. In unadjusted analyses, the inability to achieve a target hemoglobin and high-dose epoetin- were each significantly associated with increased risk of a primary endpoint (death, myocardial infarction, congestive heart failure or stroke). In adjusted models, high-dose epoetin- was associated with a significant increased hazard of a primary endpoint but the risk associated with randomization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose. Similar results were seen in the 9 month analysis. Our study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected. Prospective studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin.