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NDT Advance Access originally published online on January 14, 2008
Nephrology Dialysis Transplantation 2008 23(5):1521-1528; doi:10.1093/ndt/gfm842
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



Nonerythropoietic derivative of erythropoietin protects against tubulointerstitial injury in a unilateral ureteral obstruction model

Harumi Kitamura1, Yoshitaka Isaka1,2, Yoshitsugu Takabatake1, Ryoichi Imamura3, Chigure Suzuki1, Shiro Takahara2 and Enyu Imai1

1 Department of Nephrology 2 Department of Advanced Technology for Transplantation, 3 Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan

Correspondence and offprint requests to: Yoshitaka Isaka, Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871 Japan. Tel: +81-6-6879-3746; Fax: +81-6-6879-3749; E-mail: isaka{at}att.med.osaka-u.ac.jp



  Abstract

Background. Erythropoietin (EPO), a member of the cytokine type I superfamily, acts to increase circulating erythrocytes primarily by preventing apoptosis of erythroid progenitors, is known to protect tissues and can raise haemoglobin (Hb) concentrations. Recently, a second receptor for EPO comprising the EPO receptor and β-common receptor has been reported to mediate EPO-induced tissue protection. EPO modified by carbamylation (CEPO) only signals through this second receptor. Accordingly, we hypothesized that treatment with CEPO, which would not increase Hb concentrations, would protect against tubular damage and thereby inhibit tubulointerstitial injuries.

Methods. We evaluated therapeutic effects of CEPO using a rat unilateral ureteral obstruction model.

Results. CEPO decreased tubular apoptosis and {alpha}-smooth muscle actin ({alpha}SMA) expression in the absence of polycythaemia, while the untreated obstructed kidneys exhibited increased tubular apoptosis with expanded ({alpha}SMA) expression. While EPO treatment similarly inhibited tubular apoptosis and {alpha}SMA expression, EPO treatment increased Hb concentrations and induced a wedge-shaped infarction.

Conclusion. We established a therapeutic approach using CEPO to protect against tubulointerstitial injury. The therapeutic value of this approach warrants further attention and preclinical studies.

Keywords: apoptosis; carbamylated erythropoietin; tubulointerstitial injury; ureteral obstruction

Received for publication: 18. 5.07
Accepted in revised form: 29.10.07


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H. Kitamura and Y. Isaka
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Nephrol. Dial. Transplant., September 1, 2008; 23(9): 3033 - 3034.
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