Alteration of mRNA expression of molecules related to iron metabolism in adenine-induced renal failure rats: a possible mechanism of iron deficiency in chronic kidney disease patients on treatment.
BACKGROUND
Recombinant human erythropoietin (rHuEpo) is a definitive treatment for anaemia in chronic kidney disease (CKD). During long-term rHuEpo treatment most patients develop and show persistent iron deficiency in spite of oral iron supplementation. Abnormalities of iron absorption and transport in the duodenum may contribute to this deficiency.


METHODS
To investigate changes in iron absorption and transport in CKD and iron deficiency against the background of rHuEpo treatment, we used severely anaemic rats with adenine-induced renal failure (adenine rats) and sham-treated control rats given only the vehicle. After 4 weeks on adenine or the vehicle, the rats were divided into four groups according to whether or not they received rHuEpo for the next 4 weeks: rHuEpo(-)-adenine, rHuEpo(-)-control, rHuEpo(+)-adenine and rHuEpo(+)-control. We evaluated the effects of rHuEpo treatment on iron balance, duodenal mRNA expression of molecules related to iron absorption and transport and hepatic mRNA expression of hepcidin.


RESULTS
Treatment with rHuEpo improved anaemia and induced iron deficiency only in the adenine rats, in whom the expression of mRNAs for ferroportin 1 and hephaestin 1 increased and for divalent metal transporter 1 (DMT1) was unchanged. In contrast, control rats treated with rHuEpo showed no changes. Hepcidin mRNA expression was greater in adenine rats than in control rats.


CONCLUSIONS
In the adenine rats, rHuEpo treatment improved renal anaemia and induced persistent iron deficiency. An alteration of mRNA expression of molecules related to iron metabolism in renal insufficiency may be one of the reasons for this iron deficiency.
Hamada
Yasuhiro
Y
Division of Nephrology & Dialysis Center, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Kono
Tomoko-Nii
TN
Moriguchi
Yoshiyuki
Y
Higuchi
Masato
M
Fukagawa
Masafumi
M
D000225:Adenine; D000704:Analysis of Variance; D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D016133:Polymerase Chain Reaction; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D051437:Renal Insufficiency / Q000150:complications* / Q000503:physiopathology
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C578703:Hamp protein, rat; D064451:Hepcidins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron; D000225:Adenine