Randolph John E, Scarlett Janet M, Stokol Tracy, Saunders Kathryn M, MacLeod James N
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Am J Vet Res. 2004 Oct;65(10):1355-66. doi: 10.2460/ajvr.2004.65.1355.
To determine the activity of recombinant feline erythropoietin (rfEPO) in murine bioassays and evaluate its efficacy and safety in cats with erythropoietin-dependent nonregenerative anemia.
26 cats (group 1, 19 cats with anemia attributed to chronic kidney disease [CKD]; group 2, 7 cats with CKD and recombinant human erythropoietin [rhEPO]-induced red cell aplasia [RCA]).
The rfEPO was synthesized by use of Chinese hamster ovary (CHO) cells transfected with feline erythropoietin complementary DNA. Preclinical assessments of rfEPO included an erythroid cell proliferation assay and measurements of reticulocytosis in Balb/C mice. Clinical assessments of cats included hematologic, biochemical, and clinical examinations during 12 (group 1) or 6 (group 2) months of rfEPO treatment.
Biological activity of rfEPO was broadly equivalent to rhEPO in preclinical murine bioassays. Median Hct and absolute reticulocyte count in cats increased significantly during the first 3 weeks of rfEPO treatment, and median Hct generally could be maintained within a target range of 30% to 40% with periodic adjustments of rfEPO doses. Unexpectedly, 5 cats in group 1 and 3 cats in group 2 that initially responded to rfEPO treatment again developed anemia that was refractory to additional rfEPO treatments, even at higher doses.
Treatment with rfEPO can reestablish active erythropoiesis in most cats with CKD, even those with anemia attributable to rhEPO-induced RCA. Unfortunately, development of RCA during treatment with CHO cell-derived recombinant erythropoietin proteins was not eliminated as a serious safety concern, even for this feline-specific preparation.
在小鼠生物测定中确定重组猫促红细胞生成素（rfEPO）的活性，并评估其对依赖促红细胞生成素的非再生性贫血猫的疗效和安全性。
26只猫（第1组，19只患有慢性肾病[CKD]所致贫血的猫；第2组，7只患有CKD且因重组人促红细胞生成素[rhEPO]诱导的红细胞再生障碍[RCA]的猫）。
rfEPO通过用猫促红细胞生成素互补DNA转染的中国仓鼠卵巢（CHO）细胞合成。rfEPO的临床前评估包括红系细胞增殖测定和对Balb/C小鼠网织红细胞增多的测量。对猫的临床评估包括在rfEPO治疗的12个月（第1组）或6个月（第2组）期间进行血液学、生化和临床检查。
在临床前小鼠生物测定中，rfEPO的生物活性与rhEPO大致相当。在rfEPO治疗的前3周，猫的平均血细胞比容（Hct）和绝对网织红细胞计数显著增加，通过定期调整rfEPO剂量，平均Hct通常可维持在30%至40%的目标范围内。出乎意料的是，第1组的5只猫和第2组的3只猫最初对rfEPO治疗有反应，但后来再次出现贫血，即使给予更高剂量的rfEPO治疗也无效。
rfEPO治疗可使大多数患有CKD的猫恢复活跃的红细胞生成，即使是那些因rhEPO诱导的RCA而贫血的猫。不幸的是，即使是这种猫特异性制剂，使用CHO细胞衍生的重组促红细胞生成素蛋白治疗期间RCA的发生仍是一个严重的安全问题。
