Background. Previous reports on the renoprotective effect of erythropoietin (EPO) in the setting of chronic kidney disease (CKD) have yielded conflicting results. The aim of this study is to clarify the effect of low, non-hematopoietic dose of EPO on the evolution of diabetic nephropathy (DN) in rat model. Methods. Low dose of recombinant human EPO (150 U/kg, s.c. three times/week) was given to streptozotocin (STZ)-induced diabetic rats in two schedules; in the first one, EPO was given from day 2 after STZ injection till the end of the study (28 weeks) as prophylactic treatment; and in the other schedule EPO was given after development of DN (last 8 weeks) as therapeutic treatment. Albuminuria, blood pressure, creatinine clearance, renal venous oxygen tension (vPO2), plasma EPO, hematocrit and renal histopathology were assessed. Results. Unexpectedly, 28 weeks administration of EPO to diabetic rats led to aggravation of albuminuria and worsening of histopathological damage in spite of partial correction of renal hypoxia. Contrary to this, terminal 8 weeks EPO therapy of DN reduced albuminuria and demonstrated some favorable effects on biochemical changes and histologic picture. Conclusion. Low dose EPO exerted differential effects in rat model of DN according to treatment duration. In addition, findings of the present study warrants further investigations of the exact renoprotective role of EPO in diabetic patients with CKD who receive EPO therapy for long periods.
Erythropoietin, Diabetic nephropathy, Renal hypoxia, Albuminuria
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