Darbepoetin alfa in patients With advanced CKD Without diabetes: Randomized, controlled trial

Abstract

Background and objectives Large, randomized, controlled trials targeting higher hemoglobin level With erythropoiesis-stimulating agents for Western patients With CKD showed harm. However, the effect of anemia correction using erythropoiesis-stimulating agents may differ between CKD subpopulations. The Prevention of ESKD by Darbepoetin Alfa in CKD Patients With Non-diabetic Kidney Disease study, a multicenter, randomized, open-label, parallel-group study, aimed to examine the effect of targeting hemoglobin levels of 11–13 g/dl using darbepoetin alfa With reference to a low-hemoglobin target of 9–11 g/dl on kidney outcome in patients With advanced CKD Without diabetes in Japan. Design, setting, participants, & measurements We enrolled 491 patients With CKD Without diabetes, and an eGFR of 8–20 ml/min per 1.73 m2. Of these 491 patients, 239 and 240 Were ultimately assigned to the high-and lowhemoglobin groups, respectively (12 patients Were excluded). The primary outcome Was a kidney composite end point (starting maintenance dialysis, kidney transplantation, eGFR≤6 ml/min per 1.73 m2, and 50% reduction in eGFR). Results Mean hemoglobin levels Were 11.2±1.1 and 10.0±0.9 g/dl in the high-and low-hemoglobin groups, respectively, during the mean study period of 73.5629.7 Weeks. The kidney composite end point occurred in 105 (44%) and 116 (48%) patients in the high-and low-hemoglobin groups, respectively (log-ranktest; P50.32). The adjusted Cox proportional hazards model showed that the hazard ratio for the high-versus low-hemoglobin group Was 0.78 (95% confidence interval, 0.60 to 1.03; P50.08). Cardiovascular events occurred in 19 (8%) and 16 (7%) patients in each group, respectively, With no significant between-group difference (log-rank test; P50.66). Conclusions Targeting a higher hemoglobin level (11–13 g/dl) With darbepoetin alfa did not improve kidney outcome compared With targeting a lower hemoglobin level (9–11 g/dl) in patients With advanced CKD Without diabetes.