Kuriyama S, Tomonari H, Yoshida H, Hashimoto T, Kawaguchi Y, Sakai O
Division of Nephrology, Saiseikai Central Hospital, Tokyo, Japan.
Nephron. 1997;77(2):176-85. doi: 10.1159/000190270.
Therapy with human recombinant erythropoietin (EPO) has been accepted as effective for renal anemia in dialysis patients. However, studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction. In humans, however, the effect of EPO on residual renal function is a matter of controversy. We, therefore, investigated whether the long-term administration of EPO to predialysis patients influences residual renal function. Anemic patients at the predialysis stage with a serum creatinine (Cr) concentration ranging from 2 to 4 (average 2.9) mg/dl and a hematocrit (Ht) of less than 30% were randomly assigned to two groups which consisted of anemic patients not treated with EPO (group I, untreated anemic controls, n = 31) and anemic patients treated with EPO (group II, treated anemics, n = 42). Patients with nonsevere or moderate anemia (Ht > 30%) with a Cr ranging from 2 to 4 (average 2.6) mg/dl were also recruited as nonanemic controls (group III, untreated nonanemic controls, n = 35). Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors. All patients were kept strictly on a low-protein (0.6 g/kg/day) and a low-salt (7 g/day) diet. The degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups. The primary end point for each patient was a doubling of the baseline Cr which yielded cumulative renal survival rates which were plotted against time. Ht rose significantly from 27.0+/-2.3 to 32.1+/-3.2% in group II (n = 42, p < 0.001) with a rate of increase of 0.4+/-0.06%/week. However, it declined from 27.9+/-1.8 to 25.3+/-1.9% in group I (n = 31, p < 0.001) and from 35.9+/-3.5 to 32.2+/-3.9% in group III (n = 35, p < 0.001). Cr doubled in 26 patients (84%) in group I as compared with 22 (52%) in group II and 21 (60%) in group III. The cumulative renal survival rates in groups II and III were significantly better than that in group I: p = 0.0003 (group I vs. group II) and p = 0.0024 (group I vs. group III). However, there was no difference in the renal survival rate between groups II and III (p = 0.3111). The better survival rate obtained in group II was attributable to the better survival rate for the nondiabetic patients in this group. The present study suggests that anemia, per se, is a factor in the progression of end-stage renal failure and that reversal of anemia by EPO can retard the progression of renal failure, especially in nondiabetic patients, provided that blood pressure control, rate of increase in Ht, and dietary protein restriction are appropriate.
人重组促红细胞生成素（EPO）治疗已被公认为对透析患者的肾性贫血有效。然而，大鼠研究表明，用EPO纠正贫血可能会影响肾功能不全的进展。然而，在人类中，EPO对残余肾功能的影响仍存在争议。因此，我们研究了对透析前患者长期给予EPO是否会影响残余肾功能。将透析前阶段血清肌酐（Cr）浓度为2至4（平均2.9）mg/dl且血细胞比容（Ht）低于30%的贫血患者随机分为两组，一组为未接受EPO治疗的贫血患者（I组，未治疗的贫血对照组，n = 31），另一组为接受EPO治疗的贫血患者（II组，治疗的贫血患者，n = 42）。血清肌酐浓度为2至4（平均2.6）mg/dl、非重度或中度贫血（Ht>30%）的患者也被招募为非贫血对照组（III组，未治疗的非贫血对照组，n = 35）。通过联合使用钙拮抗剂和血管紧张素转换酶抑制剂，使三组患者的血压得到相同程度的控制。所有患者严格维持低蛋白（0.6 g/kg/天）和低盐（7 g/天）饮食。三组患者的饮食蛋白控制程度、血压控制程度以及血管紧张素转换酶抑制剂的给药频率相当。每位患者的主要终点是基线Cr翻倍，由此得出累积肾脏生存率，并将其与时间作图。II组（n = 42）的Ht从27.0±2.3显著升至32.1±3.2%（p < 0.001），每周升高率为0.4±0.06%。然而，I组（n = 31）的Ht从27.9±1.8降至25.3±1.9%（p < 0.001），III组（n = 35）的Ht从35.9±3.5降至32.2±3.9%（p < 0.001）。I组26例患者（84%）的Cr翻倍，而II组为22例（52%），III组为21例（60%）。II组和III组的累积肾脏生存率显著优于I组：p = 0.0003（I组与II组），p = 0.0024（I组与III组）。然而，II组和III组之间的肾脏生存率无差异（p = 0.3111）。II组获得更好的生存率归因于该组非糖尿病患者更好的生存率。本研究表明，贫血本身是终末期肾衰竭进展的一个因素，并且通过EPO纠正贫血可以延缓肾衰竭的进展，尤其是在非糖尿病患者中，前提是血压控制、Ht升高率和饮食蛋白限制得当。
