Effect of purified recombinant human erythropoietin on anemia in rats with experimental renal failure induced by five-sixth nephrectomy.
Recombinant human erythropoietin (rHuEPO) was purified from the conditioned media of Chinese hamster ovary cells with a transfected human erythropoietin gene. We investigated the effects of the rHuEPO in rats with renal anemia induced by partial nephrectomy. Five-sixth nephrectomy resulted in renal failure with anemia. Twenty-five days after the operation plasma urea nitrogen was increased about 2.5 times, and the red blood cell count, hematocrit, and hemoglobin concentration fell to 85% of normal. The reticulocyte count and plasma erythropoietin level did not change such as they do in patients with anemia due to chronic renal failure. Both total red blood cell volume and the plasma iron turnover rate were depressed in five-sixth nephrectomized rats compared with normal rats. The five-sixth nephrectomized rats were injected with rHuEPO (60 IU/kg) intravenously every second day for a total of six injections. After three injections of rHuEPO, circulation volume of total red blood cells was increased from 9.9 ml to 14.6 ml, and the plasma iron turnover rate was increased from 1.03 mg/kg/day to 2.12 mg/kg/day, and the reticulocyte count was also increased. After six injections, a marked increase of the red blood cell count, hematocrit, and hemoglobin concentration were observed. Plasma urea nitrogen and the creatinine levels as indications for renal function did not change after rHuEPO administration in both normal and five-sixth nephrectomized rats. In conclusion rHuEPO has a potent erythropoietic action and it is possible to cure the anemia caused by renal failure.
Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
A
A
Kawamura
M
M
Higuchi
N
N
Imai
T
T
Kawaguchi
Y
Y
Ogura
D000740:Anemia / Q000097:blood / Q000209:etiology / Q000628:therapy*; D000818:Animals; D001772:Blood Cell Count; D001810:Blood Volume; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D012156:Reticulocytes / Q000166:cytology
D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron