The improvement of ischemia/reperfusion injury by erythropoetin is not mediated through bone marrow cell recruitment in rats.
BACKGROUND
Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment.


METHODS
Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue.


RESULTS
At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups.


CONCLUSIONS
EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.
Esposito
C
C
Unit of Nephrology, University of Pavia, Pavia, Italy. espositociro56@live.it
Pertile
E
E
Grosjean
F
F
Castoldi
F
F
Diliberto
R
R
Serpieri
N
N
Arra
M
M
Villa
L
L
Mangione
F
F
Esposito
V
V
Migotto
C
C
Valentino
R
R
Dal Canton
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D016026:Bone Marrow Transplantation; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects; D008297:Male; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D004921:Erythropoietin