Erythropoietin-induced optimization of renal function after warm ischemia.
OBJECTIVE
Recent preclinical data have indicated that erythropoietin (Epo) can protect organs from ischemic damage. We evaluated the ability of Epo to protect the kidney from the effects of ischemia.


METHODS
Thirty dogs underwent a laparoscopic nephrectomy and were allowed to recover for 2 weeks. The dogs were then divided into five groups. Animals in groups 1 and 2 underwent 1.5 hours of abdominal insufflation with placebo (saline) injection (group 1) or Epo injection (group 2) before; groups 3 to 5 underwent 1 hour of laparoscopic renal artery clamping after placebo injection (group 3), Epo injection (group 4), or mannitol injection (group 5). Serum evaluations and 24-hour urine collections were performed weekly. After 28 days, the animals were sacrificed. Statistical analysis was performed with the Kruskal-Wallis test.


RESULTS
After recovery from the initial nephrectomy, all dogs had similar serum hematocrit and creatinine levels. Hematocrit was not significantly affected by Epo administration at any time point. Immediately after the second surgery, dogs that underwent renal artery clamping (groups 3-5) had significantly lower 24-hour urine creatinine levels than those that were not clamped (groups 1-2). After 4 weeks of recovery, the dogs that had received Epo before ischemia (group 4) had recovered significantly more renal function than the dogs that received placebo or mannitol before ischemia (urine creatinine level = Epo 149.1 mg/dL v placebo 70.7 mg/dL v mannitol 80.7 mg/dL). At sacrifice, microalbuminuria was also significantly less in dogs receiving Epo before ischemia than their mannitol or placebo counterparts.


CONCLUSIONS
The current study demonstrates that administering Epo before warm ischemia can improve the recovery of renal function after ischemia better than placebo or mannitol.
Phillips
Courtney K
CK
Department of Urology, Columbia University, New York, New York, USA.
Hruby
Gregory W
GW
Mirabile
Gabriella
G
Motamedinia
Piruz
P
Lehman
Daniel S
DS
Okhunov
Zhamshid
Z
Singh
Harmanmeet
H
Schwartz
Marissa
M
Benson
Mitchell C
MC
Landman
Jaime
J
D000419:Albuminuria / Q000503:physiopathology; D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000601:surgery; D007677:Kidney Function Tests; D011994:Recombinant Proteins; D013997:Time Factors; D052096:Warm Ischemia
D011994:Recombinant Proteins; D004921:Erythropoietin; D003404:Creatinine