Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass

D. L. Garcia, Sharon Anderson, H. G. Rennke, B. M. Brenner

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, ~42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (~30 vol/dl) by feeding a low iron diet or prevented (~50 vol/dl) by administration of recombinant human erythropoietin (r-HuEpo). In functional studies performed 4 weeks after renal ablation, untreated rats exhibited mild anemia with systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Preventing anemia with r-HuEpo worsened systemic and glomerular hypertension, effects largely obviated by induction of more marked anemia with the low iron diet. Untreated rats followed for 6 weeks postablation exhibited progressive proteinuria and sclerosis involving 12% of glomeruli, contrasted with 33% in rats given r-HuEpo. Even after 12 weeks, sclerosis involved only 6% of glomeruli in rats with more severe anemia but progressed to 30% in untreated rats. Thus, anemia limits systemic and glomerular hypertension and glomerular injury, whereas its prevention by r-HuEpo severely accelerates hemodynamically mediated glomerular injury in this model. These results suggest that anemia is a hemodynamically favorable adaptation to chronic renal disease and that its overly vigorous correction may have adverse renal hemodynamic and structural consequences.

Original languageEnglish (US)
Pages (from-to)6142-6146
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number16
StatePublished - 1988
Externally publishedYes

Fingerprint

Erythropoietin
Anemia
Hypertension
Kidney
Wounds and Injuries
Sclerosis
Chronic Renal Insufficiency
Iron
Hemodynamics
Diet
Nephrons
Nephrectomy
Glomerular Filtration Rate
Hematocrit
Proteinuria
Wistar Rats

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{3aec647074bb433aa086a528d05fffe6,
title = "Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass",
abstract = "Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, ~42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (~30 vol/dl) by feeding a low iron diet or prevented (~50 vol/dl) by administration of recombinant human erythropoietin (r-HuEpo). In functional studies performed 4 weeks after renal ablation, untreated rats exhibited mild anemia with systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Preventing anemia with r-HuEpo worsened systemic and glomerular hypertension, effects largely obviated by induction of more marked anemia with the low iron diet. Untreated rats followed for 6 weeks postablation exhibited progressive proteinuria and sclerosis involving 12{\%} of glomeruli, contrasted with 33{\%} in rats given r-HuEpo. Even after 12 weeks, sclerosis involved only 6{\%} of glomeruli in rats with more severe anemia but progressed to 30{\%} in untreated rats. Thus, anemia limits systemic and glomerular hypertension and glomerular injury, whereas its prevention by r-HuEpo severely accelerates hemodynamically mediated glomerular injury in this model. These results suggest that anemia is a hemodynamically favorable adaptation to chronic renal disease and that its overly vigorous correction may have adverse renal hemodynamic and structural consequences.",
author = "Garcia, {D. L.} and Sharon Anderson and Rennke, {H. G.} and Brenner, {B. M.}",
year = "1988",
language = "English (US)",
volume = "85",
pages = "6142--6146",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "16",

}

TY - JOUR

T1 - Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass

AU - Garcia, D. L.

AU - Anderson, Sharon

AU - Rennke, H. G.

AU - Brenner, B. M.

PY - 1988

Y1 - 1988

N2 - Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, ~42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (~30 vol/dl) by feeding a low iron diet or prevented (~50 vol/dl) by administration of recombinant human erythropoietin (r-HuEpo). In functional studies performed 4 weeks after renal ablation, untreated rats exhibited mild anemia with systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Preventing anemia with r-HuEpo worsened systemic and glomerular hypertension, effects largely obviated by induction of more marked anemia with the low iron diet. Untreated rats followed for 6 weeks postablation exhibited progressive proteinuria and sclerosis involving 12% of glomeruli, contrasted with 33% in rats given r-HuEpo. Even after 12 weeks, sclerosis involved only 6% of glomeruli in rats with more severe anemia but progressed to 30% in untreated rats. Thus, anemia limits systemic and glomerular hypertension and glomerular injury, whereas its prevention by r-HuEpo severely accelerates hemodynamically mediated glomerular injury in this model. These results suggest that anemia is a hemodynamically favorable adaptation to chronic renal disease and that its overly vigorous correction may have adverse renal hemodynamic and structural consequences.

AB - Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, ~42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (~30 vol/dl) by feeding a low iron diet or prevented (~50 vol/dl) by administration of recombinant human erythropoietin (r-HuEpo). In functional studies performed 4 weeks after renal ablation, untreated rats exhibited mild anemia with systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Preventing anemia with r-HuEpo worsened systemic and glomerular hypertension, effects largely obviated by induction of more marked anemia with the low iron diet. Untreated rats followed for 6 weeks postablation exhibited progressive proteinuria and sclerosis involving 12% of glomeruli, contrasted with 33% in rats given r-HuEpo. Even after 12 weeks, sclerosis involved only 6% of glomeruli in rats with more severe anemia but progressed to 30% in untreated rats. Thus, anemia limits systemic and glomerular hypertension and glomerular injury, whereas its prevention by r-HuEpo severely accelerates hemodynamically mediated glomerular injury in this model. These results suggest that anemia is a hemodynamically favorable adaptation to chronic renal disease and that its overly vigorous correction may have adverse renal hemodynamic and structural consequences.

UR - http://www.scopus.com/inward/record.url?scp=0000313513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0000313513&partnerID=8YFLogxK

M3 - Article

C2 - 3413082

AN - SCOPUS:0000313513

VL - 85

SP - 6142

EP - 6146

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 16

ER -