Plasma erythropoietin level in rats after kidney proximal tubular impairment

The involvement of proximal kidney tubules in erythropoietin production and/or in its control has been a subject of controversy among researchers. The present study addresses the problem whether acute tubular impairment affects erythropoietin production and thus alters the basic hematological parameters. For this purpose rats with hypobaric hypoxia-stimulated (42.55 kPa) erythropoesis were studied and the rat model of gentamicin-induced (50 mg/kg daily for 15 days) tubular damage was employed. According to the study protocol 4 different groups of rats were used: control rats, rats exposed to hypobaric hypoxia, rats treated with gentamicin prior to hypoxic exposure and finally rats given a dose of 50 U human recombinant erythropoietin for 2 days following treatment with gentamicin. The evaluated hematological parameters included: hemoglobin and hematocrit levels, reticulocyte count and plasma creatinine concentration. Histological analysis of kidney sections was also used. INCSTAR (USA) immunoassay was employed to determine plasma erythropoietin level. Evidence (histological and laboratory-elevated plasma creatinine) of distinct tubular lesions was found in rats injected with gentamicin. Hemoglobin and hematocrit levels were decreased in rats treated with gentamicin but a rise in reticulocyte count was seen on day 3 after hypoxic exposure--39@1000 +/- 10 vs. 5@1000 +/- 1.3 on day 0 (p < 0.001). Reduced reticulocyte counts on day 0 were not seen only in rats injected with human recombinant erythropoietin--36.33@1000 (p < 0.01). Hypoxia-induced increase in plasma erythropoietin was inhibited in animals treated with gentamicin--15.3 mU/ml (on day 0). Both hypoxic exposure and erythropoietin administration were associated with a rise in plasma erythropoietin on day 0--40.5 +/- 4.4 mU/ml and 42.7 +/- 4.1 mU/ml respectively, which normalised on day 3. The results of the study support the hypothesis that the erythropoietin response in rats after stimulation is related to the functional condition of the proximal kidney tubules.