Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Japan.
Department of Nephrology, Nagoya University, Nagoya, Japan.
Clin J Am Soc Nephrol. 2020 May 7;15(5):608-615. doi: 10.2215/CJN.08900719. Epub 2020 Apr 3.
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 m. Of these 491 patients, 239 and 240 were ultimately assigned to the high- and low-hemoglobin 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 m, and 50% reduction in eGFR).
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 73.5±29.7 weeks. The kidney composite end point occurred in 105 (44%) and 116 (48%) patients in the high- and low-hemoglobin groups, respectively (log-rank test; =0.32). 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; =0.08). Cardiovascular events occurred in 19 (8%) and 16 (7%) patients in each group, respectively, with no significant between-group difference (log-rank test; =0.66).
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.
Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease (PREDICT), NCT01581073.
针对西方慢性肾脏病（CKD）患者，应用促红细胞生成素刺激剂（ESA）提高血红蛋白水平的大型随机对照试验显示存在危害。然而，ESA 纠正贫血的效果可能因 CKD 亚组而有所不同。在日本，一项多中心、随机、开放标签、平行分组研究——预防非糖尿病肾病患者慢性肾脏病进入终末期肾病的达贝泊汀 α 研究（Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease study，PREDICT）旨在探讨与较低的血红蛋白目标（9-11 g/dl）相比，使用达贝泊汀 α 将血红蛋白水平目标设定为 11-13 g/dl 对晚期 CKD 且无糖尿病患者的肾脏结局的影响。
设计、设置、参与者和测量：我们纳入了 491 例 CKD 且无糖尿病、eGFR 为 8-20 ml/min/1.73 m2 的患者。在这 491 例患者中，最终分别有 239 例和 240 例被分配到高血红蛋白组和低血红蛋白组（排除 12 例患者）。主要结局为肾脏复合终点（开始维持性透析、肾脏移植、eGFR≤6 ml/min/1.73 m2 和 eGFR 降低 50%）。
在平均 73.5±29.7 周的研究期间，高血红蛋白组和低血红蛋白组的平均血红蛋白水平分别为 11.2±1.1 和 10.0±0.9 g/dl。高血红蛋白组和低血红蛋白组的肾脏复合终点分别发生在 105（44%）和 116（48%）例患者中（对数秩检验；=0.32）。校正后的 Cox 比例风险模型显示，高血红蛋白组与低血红蛋白组的风险比为 0.78（95%置信区间，0.60 至 1.03；=0.08）。每组各有 19 例（8%）和 16 例（7%）患者发生心血管事件，两组间无显著差异（对数秩检验；=0.66）。
与目标血红蛋白水平（9-11 g/dl）相比，使用达贝泊汀 α 将目标血红蛋白水平设定为 11-13 g/dl 并不能改善晚期 CKD 且无糖尿病患者的肾脏结局。
预防非糖尿病肾病患者慢性肾脏病进入终末期肾病的达贝泊汀 α 研究（Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease，PREDICT），NCT01581073。
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