Erythropoietin-Induced Optimization of Renal Function After Warm Ischemia

被引:7
作者
Phillips, Courtney K. [1 ]
Hruby, Gregory W. [1 ]
Mirabile, Gabriella [1 ]
Motamedinia, Piruz [1 ]
Lehman, Daniel S. [1 ]
Okhunov, Zhamshid [1 ]
Singh, Harmanmeet [1 ]
Schwartz, Marissa [1 ]
Benson, Mitchell C. [1 ]
Landman, Jaime [1 ]
机构
[1] Columbia Univ, Dept Urol, New York, NY 10032 USA
关键词
HYPOXIA-INDUCIBLE FACTOR; REPERFUSION INJURY; FACTOR; 1-ALPHA; HIF-ALPHA; MODEL; KIDNEY; TOLERANCE; PROTECTS; HYDROXYLATION; DYSFUNCTION;
D O I
10.1089/end.2008.0183
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background and Purpose: 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 upsilon placebo 70.7 mg/dL upsilon mannitol 80.7 mg/dL). At sacrifice, microalbuminuria was also significantly less in dogs receiving Epo before ischemia than their mannitol or placebo counterparts. Conclusion: The current study demonstrates that administering Epo before warm ischemia can improve the recovery of renal function after ischemia better than placebo or mannitol.
引用
收藏
页码:359 / 365
页数:7
相关论文
共 33 条
[1]   Erythropoietin mimics ischemic preconditioning [J].
Baker, JE .
VASCULAR PHARMACOLOGY, 2005, 42 (5-6) :233-241
[2]   Laparoscopic warm renal ischemia in the solitary porcine kidney model [J].
Baldwin, DD ;
Maynes, LJ ;
Berger, KA ;
Desai, PJ ;
Zuppan, CW ;
Zimmerman, GJ ;
Winkielman, AM ;
Sterling, TH ;
Tsai, CK ;
Ruckle, HC .
UROLOGY, 2004, 64 (03) :592-597
[3]   Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury [J].
Cai, ZQ ;
Manalo, DJ ;
Wei, G ;
Rodriguez, ER ;
Fox-Talbot, K ;
Lu, HS ;
Zweier, JL ;
Semenza, GL .
CIRCULATION, 2003, 108 (01) :79-85
[4]   PROTECTION OF KIDNEYS FROM WARM ISCHEMIC-INJURY - DOSAGE AND TIMING OF MANNITOL ADMINISTRATION [J].
COLLINS, GM ;
GREEN, RD ;
BOYER, D ;
HALASZ, NA .
TRANSPLANTATION, 1980, 29 (01) :83-84
[5]   Functional activation of heat shock factor and hypoxia-inducible factor in the kidney [J].
Eickelberg, O ;
Seebach, F ;
Riordan, M ;
Thulin, G ;
Mann, A ;
Reidy, KH ;
Van Why, SK ;
Kashgarian, M ;
Siegel, N .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2002, 13 (08) :2094-2101
[6]  
Feldser D, 1999, CANCER RES, V59, P3915
[7]  
GRUNDMANN R, 1977, SURGERY, V81, P542
[8]   Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy:: randomised, double-blind, placebo-controlled trial [J].
Henke, M ;
Laszig, R ;
Rübe, C ;
Schäfer, U ;
Haase, KD ;
Schilcher, B ;
Mose, S ;
Beer, KGT ;
Burger, U ;
Dougherty, C ;
Frommhold, H .
LANCET, 2003, 362 (9392) :1255-1260
[9]   Erythropoietin just before reperfusion reduces both lethal arrhythmias and infarct size via the phosphatidylinositol-3 kinase-dependent pathway in canine hearts [J].
Hirata, A ;
Minamino, T ;
Asanuma, H ;
Sanada, S ;
Fujita, M ;
Tsukamoto, O ;
Wakeno, M ;
Myoishi, M ;
Okada, K ;
Koyama, H ;
Komamura, K ;
Takashima, S ;
Shinozaki, Y ;
Mori, H ;
Tomoike, H ;
Hori, M ;
Kitakaze, M .
CARDIOVASCULAR DRUGS AND THERAPY, 2005, 19 (01) :33-40
[10]   Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs [J].
Hirata, Akio ;
Minammo, Tetsuo ;
Asanuma, Hiroshi ;
Fujita, Masashi ;
Wakeno, Masakatsu ;
Myoishi, Masafumi ;
Tsukamoto, Osamu ;
Okada, Ken-ichiro ;
Koyama, Hidekazu ;
Komamura, Kazuo ;
Takashima, Seiji ;
Shinozaki, Yoshiro ;
Mori, Hidezo ;
Shiraga, Masamichi ;
Kitakaze, Masafumi ;
Hori, Masatsugu .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2006, 48 (01) :176-184