How Erythropoietin Affects Bone Marrow of Uremic Patients

Abstract

In a prospective study, 40 maintenance hemodialysis patients, randomized in two equal groups, were treated with recombinant human erythropoietin (rHuEPO) for their renal anemia, for a period of 2 years. One group was treated for 2 years, while the other was untreated control during the first year, but received rHuEPO during the second year of the study. Anemia was corrected in all treated patients and hematocrit maintained between 30 and 35 vol% by low-dose subcutaneous treatment with Recormon® (Boehringer Mannheim GmbH, Germany), according to the study protocol. Bone marrow biopsy (BMB), from the posterior iliac crest, was taken by the method of Jam-shidi from 32 patients. Fourteen patients from the control group were biopsied twice: once at baseline and the second time at 12 months of treatment, while 15 patients from the other group were biopsied only once, at 24 months of rHuEPO treatment. The biopsies were embedded in wax and in epoxy resin, and after staining for light and electron microscopy, they were semiquantitatively examined for several parameters: cellularity, myeloid:erythroid (M:E) ratio, megakaryocytes, fatty tissue, megaloblasts, and marrow iron. Cellularity of the bone marrow increased significantly at 12 months of treatment and it remained so at 24 months. M:E ratio was significantly reduced indicating expansion of the erythroid pool, both at 12 and 24 months of therapy. The number of megakaryocytes in the bone marrow increased significantly at 12 months and remained high at 24 months of treatment, while fatty tissue was significantly reduced at 12 and 24 months compared to the baseline values. There was no significant change in the percentage of megaloblasts in the bone marrow. Hemosiderin was reduced after treatment indicating mobilization of the bone marrow iron stores upon treatment with rHuEPO. We concluded that rHuEPO had a beneficial long-term effect on bone marrow.

Macrocytosis may be associated with mortality in chronic hemodialysis patients: a prospective study

“…However, altered hematopoiesis was not confirmed with bone marrow biopsy in this study. Furthermore, bone marrow dysplasia was not identified in an earlier study of dialysis patients treated with recombinant erythropoietin for 24 months who subsequently underwent bone marrow biopsy [32]. In addition, macrocytosis in dialysis patients has been identified prior to the introduction of ESAs [17].…”

Erythroid proliferations in myeloid neoplasms

“…Close attention to the clinical history is critical in distinguishing reactive from neoplastic erythroid proliferations. Patients with anemia treated with erythropoietin may show transient erythroid hyperplasia; however, the erythroblast percentage rarely excess 50% of total bone marrow cellular elements in such cases [49,50]. In MDS patients who respond to erythropoietin treatment, the erythroblast proportion is often decreased rather than increased, in parallel to decreased overall bone marrow apoptosis and recovered more effective erythropoiesis [51,52].…”

Assessment of Erythropoietin Levels and Some Iron Indices in Chronic Renal Failure and Liver Cirrhosis Patients

“…Renal anaemia is of multifactorial etiology. The main factor, however, is decreased erythropoietin (EPO) production by the failed kidneys [3][4][5][6][7][8][9].…”