α-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Model

被引:22
作者
Simmons, Matthew N. [1 ]
Subramanian, Vairavan [1 ]
Crouzet, Sebastien [1 ]
Haber, Georges-Pascal [1 ]
Colombo, Jose R., Jr. [2 ]
Ukimura, Osamu [3 ]
Neilsen, Soren [4 ]
Gill, Inderbir S. [5 ]
机构
[1] Cleveland Clin Fdn, Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA
[2] Univ Sao Paulo, Dept Urol, Sao Paulo, Brazil
[3] Kyoto Prefectural Univ Med, Kyoto, Japan
[4] Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark
[5] Univ So Calif, Inst Urol, Los Angeles, CA USA
关键词
kidney; nephrectomy; AP214; ischemia; ACUTE-RENAL-FAILURE; WARM ISCHEMIA; RECEPTORS; NEPHRECTOMY; PEPTIDES;
D O I
10.1016/j.juro.2009.12.007
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
Purpose: alpha-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of a-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates. Materials and Methods: We performed a prospective, blinded, randomized, placebo controlled study in 26 pigs. Laparoscopic technique was used for left nephrectomy and to induce complete warm ischemia in the right kidney for 120 minutes. AP214 (200 mu g/kg intravenously) was administered daily on the day of surgery and for 5 days thereafter. Kidney function was measured for 9 days. We measured changes in serum creatinine, estimated glomerular filtration rate, serum C-reactive protein and urine interleukin-18. Results: In the placebo control and AP214 groups mean peak serum creatinine was 10.2 vs 3.92 mg/dl and the estimated glomerular filtration rate nadir was 22.9 vs 62.6 ml per minute per kg (each p = 0.001). Functional nadir occurred at 72 vs 24 hours in the control vs AP214 groups. Estimated glomerular filtration rate outcome on postoperative day 9 was 118 vs 156 ml per minute per kg in the control vs AP214 groups (p = 0.04). Conclusions: We noted a robust renoprotective effect of AP214. A similar AP214 effect may be observed in humans. Future research includes mechanistic studies in pigs and a phase II human clinical trial of AP214 in kidney transplant and partial nephrectomy populations.
引用
收藏
页码:1625 / 1629
页数:5
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