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Hematopoietic progenitors in children with end-stage renal disease
Y Barak1, L Sinai-Treiman, Y Karov
1Institute for Pediatric Research, Kaplan Hospital, Rehovot, Israel.
Insights
Children with end-stage renal disease (ESRD) have more erythroid progenitors (BFU-E) that respond better to erythropoietin. Recombinant human erythropoietin (rHuEpo) therapy normalized these progenitor cells in anemic ESRD patients.
Area of Science:
- Pediatric Nephrology
- Hematology
- Cell Biology
Background:
- Anemia is common in children with end-stage renal disease (ESRD).
- Erythroid progenitors, specifically burst-forming unit-erythroid (BFU-E), are crucial for red blood cell production.
- Understanding the behavior of BFU-E in pediatric ESRD is vital for managing anemia.
Purpose of the Study:
- To investigate the abundance and responsiveness of erythroid progenitors (BFU-E) in anemic children with ESRD.
- To assess the effect of recombinant human erythropoietin (rHuEpo) therapy on these progenitor cells.
- To determine the presence of any uremic inhibitors of erythropoiesis.
Main Methods:
- Quantified bone marrow and circulating BFU-E in anemic children with ESRD and age-matched controls.
- Assessed in vitro responsiveness of BFU-E to varying concentrations of rHuEpo.
- Monitored changes in BFU-E after 4 weeks of rHuEpo therapy.
- Evaluated granulocyte-monocyte progenitor numbers and in vitro erythropoiesis inhibition assays.
Main Results:
- BFU-E were significantly more abundant (2.0-fold in bone marrow, 1.9-fold in circulation) and responsive to low-dose rHuEpo in ESRD patients compared to controls.
- rHuEpo therapy normalized both the number and in vitro responsiveness of circulating BFU-E after 4 weeks.
- Granulocyte-monocyte progenitor levels were comparable between ESRD patients and controls, both before and after therapy.
- No evidence of uremic inhibitors affecting erythropoiesis was found in patient serum or conditioned media.
Conclusions:
- Anemic children with ESRD exhibit an increased number and heightened sensitivity of BFU-E to rHuEpo.
- rHuEpo therapy effectively corrects the abnormalities in BFU-E in pediatric ESRD.
- The anemia in these patients is not due to uremic inhibitors of erythropoiesis but rather related to progenitor cell dynamics.
Abstract:
Bone marrow and circulating erythroid progenitors (BFU-E) in six anemic children with end-stage renal disease (ESRD) were 2.0 and 1.9 times as abundant, respectively, as in six age-matched normal controls and were significantly more responsive in vitro to low concentrations of recombinant human erythropoietin (rHuEpo) than those from the controls. After 4 weeks of rHuEpo therapy, both the number and the in vitro rHuEpo response of circulating BFU-E in the ESRD patients returned to normal control values. The numbers of bone marrow and circulating granulocyte-monocyte progenitors in the ESRD patients before and after rHuEpo therapy were comparable to those of normal controls. There was no inhibition of in vitro erythropoiesis by either the patients' serum or medium conditioned by their mononuclear cells. These results demonstrate a significant abundance and an increased rHuEpo sensitivity of BFU-E in anemic children with ESRD with no evidence of the presence of uremic inhibitors to erythropoiesis.