Anemia lessens and its prevention with recombinant human erythropoietin worsens glomerular injury and hypertension in rats with reduced renal mass.
Chronic renal disease is frequently characterized by anemia, which may modify systemic and renal hemodynamics. In adult Munich-Wistar rats, the mild anemia (hematocrit, approximately equal to 42 vol/dl) that accompanies five-sixths nephrectomy was either made more severe (approximately equal to 30 vol/dl) by feeding a low iron diet or prevented (approximately equal to 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.
Garcia
D L
DL
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Anderson
S
S
Rennke
H G
HG
Brenner
B M
BM
D000740:Anemia / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001809:Blood Viscosity; D004921:Erythropoietin / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D006400:Hematocrit; D006973:Hypertension / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D004921:Erythropoietin