The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo

J. W. Eschbach, Jeanette Mladenovic, J. F. Garcia, P. W. Wahl, J. W. Adamson

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma my contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.

Original languageEnglish (US)
Pages (from-to)434-441
Number of pages8
JournalJournal of Clinical Investigation
Volume74
Issue number2
StatePublished - 1984
Externally publishedYes

Fingerprint

Erythropoietin
Chronic Kidney Failure
Anemia
Sheep
Uremia
Erythropoiesis
Reticulocytes
Iron
Erythrocyte Aging
Hemoglobin C
Polycythemia
Phlebotomy
Nephrectomy
Erythrocytes
Bone Marrow
Kidney

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Eschbach, J. W., Mladenovic, J., Garcia, J. F., Wahl, P. W., & Adamson, J. W. (1984). The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo. Journal of Clinical Investigation, 74(2), 434-441.

The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo. / Eschbach, J. W.; Mladenovic, Jeanette; Garcia, J. F.; Wahl, P. W.; Adamson, J. W.

In: Journal of Clinical Investigation, Vol. 74, No. 2, 1984, p. 434-441.

Research output: Contribution to journalArticle

Eschbach, JW, Mladenovic, J, Garcia, JF, Wahl, PW & Adamson, JW 1984, 'The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo', Journal of Clinical Investigation, vol. 74, no. 2, pp. 434-441.
Eschbach, J. W. ; Mladenovic, Jeanette ; Garcia, J. F. ; Wahl, P. W. ; Adamson, J. W. / The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo. In: Journal of Clinical Investigation. 1984 ; Vol. 74, No. 2. pp. 434-441.
@article{91de551fd02744cc907bc2e0ae1aecdc,
title = "The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo",
abstract = "The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma my contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.",
author = "Eschbach, {J. W.} and Jeanette Mladenovic and Garcia, {J. F.} and Wahl, {P. W.} and Adamson, {J. W.}",
year = "1984",
language = "English (US)",
volume = "74",
pages = "434--441",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "2",

}

TY - JOUR

T1 - The anemia of chronic renal failure in sheep. Response to erythropoietin-rich plasma in vivo

AU - Eschbach, J. W.

AU - Mladenovic, Jeanette

AU - Garcia, J. F.

AU - Wahl, P. W.

AU - Adamson, J. W.

PY - 1984

Y1 - 1984

N2 - The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma my contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.

AB - The hypoproliferative anemia in chronic renal failure has been assumed to be the result of decreased erythropoietin (Ep) production by the damaged kidney and of the shortening of erythrocyte survival. However, many in vitro studies suggest that erythropoietic inhibitors in uremic plasma my contribute to the anemia. To determine the in vivo relevance of uremic inhibitors, increasing amounts of Ep as Ep-rich plasma were infused into six uremic sheep, and their erythropoietic responses were compared with those of nine normal sheep receiving similar amounts of Ep-rich plasma. Three sheep were studied in both normal and uremic states. Ep-rich plasma was obtained from phenylhydrazine- and phlebotomy-induced anemic sheep. Stable uremia was created by subtotal nephrectomy. Erythropoiesis was quantitated by reticulocyte response, ferrokinetics (plasma iron turnover and marrow transit time), and by hemoglobin C synthesis. Ep-rich plasma stimulated erythropoiesis similarly in uremic and normal sheep, regardless of the degree of uremia. Nondialyzed uremic sheep responded as well as dialyzed animals. The anemia was corrected in the uremic sheep after 15-40 daily infusions of Ep-rich plasma, the total dosage depending on the severity of the anemia. Polycythemia was induced when the infusions were continued. Reticulocytes, plasma iron turnover, and erythrocyte mass changes increased as the amount of Ep-rich plasma was increased. These dose-response effects, coupled with the identical erythropoietic response in normal and uremic sheep given the same amount of Ep-rich plasma, imply that there are no physiologically significant erythropoietic inhibitors in uremia.

UR - http://www.scopus.com/inward/record.url?scp=0021185248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021185248&partnerID=8YFLogxK

M3 - Article

C2 - 6746902

AN - SCOPUS:0021185248

VL - 74

SP - 434

EP - 441

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 2

ER -