Expression, bioactivity, and clinical assessment of recombinant feline erythropoietin.
OBJECTIVE
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.


METHODS
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]).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Randolph
John E
JE
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Scarlett
Janet M
JM
Stokol
Tracy
T
Saunders
Kathryn M
KM
MacLeod
James N
JN
D000740:Anemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000662:veterinary*; D000818:Animals; D001681:Biological Assay / Q000662:veterinary; D001772:Blood Cell Count / Q000662:veterinary; D001774:Blood Chemical Analysis / Q000662:veterinary; D001854:Bone Marrow Cells; D016466:CHO Cells; D002371:Cat Diseases / Q000188:drug therapy / Q000378:metabolism*; D002415:Cats; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000662:veterinary*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D013997:Time Factors; D014162:Transfection / Q000662:veterinary
D017931:DNA Primers; D018076:DNA, Complementary; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin