title: Alpha-melanocyte stimulating hormone analogue AP214 protects against ischemia induced acute kidney injury in a porcine surgical model.
abstract: OBJECTIVE
  alpha-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of alpha-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates.
  
  
  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 microg/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.
authors.affiliation: Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. Simmonm2@ccf.org
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Simmons
authors.forename: Vairavan
authors.initials: V
authors.lastname: Subramanian
authors.forename: Sebastien
authors.initials: S
authors.lastname: Crouzet
authors.forename: Georges-Pascal
authors.initials: GP
authors.lastname: Haber
authors.forename: Jose R
authors.initials: JR
authors.lastname: Colombo
authors.forename: Osamu
authors.initials: O
authors.lastname: Ukimura
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Søren
authors.initials: S
authors.lastname: Neilsen
authors.forename: Inderbir S
authors.initials: IS
authors.lastname: Gill
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D009392:Nephrectomy; D013552:Swine; D052096:Warm Ischemia; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C530134:AP 214; D000521:alpha-MSH