Potential for erythropoietin synthesis in kidney of uraemic rat alters depending on severity of renal failure.
OBJECTIVE
Renal anaemia is a common early complication of chronic renal failure (CRF) that is characterized by relative erythropoietin (EPO) deficiency. Although a lowered renal function is considered to induce limited EPO production, potential EPO production capacity in CRF remains unclear. The aim of this study was to determine the mechanisms underlying this relative deficiency.


METHODS
Male Sprague-Dawley rats were underwent 5/6 nephrectomy with different severities of CRF. These rats were assigned to two groups - mild CRF or advanced CRF - and subjected to haemodilution by exchange of blood with Ringer's solution or haemoconcentration by blood transfusion. Serum EPO and EPO transcript levels in remnant kidney were examined. Expression levels of hypoxia-related genes, including heme oxygenase-1 (HO-1) and glucose transporter-1 (Glut-1), were also examined.


RESULTS
Haemodilution increased both serum EPO and EPO transcript levels in mild CRF, as observed in sham-operated controls, whereas the extents of such increases were significantly smaller in advanced CRF. HO-1 and Glut-1 transcript levels also increased by haemodilution in mild CRF, but not in advanced CRF. Haemoconcentration markedly decreased serum EPO and EPO transcript levels in mild CRF as in controls. Rats with advanced CRF did not survive after blood transfusion.


CONCLUSIONS
Potential EPO regulation capacity in mild CRF is as conserved as that in normal control, whereas that in advanced CRF is impaired, suggesting that underlying mechanisms of low EPO production alters according to the stage of CRF.
Sanada
Satoru
S
Division of Molecular Medicine, Centre for Translational and Advanced Animal Research, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
Toyama
Hiroaki
H
Ejima
Yutaka
Y
Matsubara
Mitsunobu
M
D000818:Animals; D004921:Erythropoietin / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000378:metabolism*
D004921:Erythropoietin