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

Matthew N. Simmons, Vairavan Subramanian, Sebastien Crouzet, Georges Pascal Haber, Jose R. Colombo, Osamu Ukimura, Søren Neilsen, Inderbir S. Gill

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Purpose: α-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of α-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 μg/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.

Original languageEnglish (US)
Pages (from-to)1625-1629
Number of pages5
JournalJournal of Urology
Volume183
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

Keywords

  • AP214
  • ischemia
  • kidney
  • nephrectomy

ASJC Scopus subject areas

  • Urology

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