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 language | English (US) |
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Pages (from-to) | 1625-1629 |
Number of pages | 5 |
Journal | Journal of Urology |
Volume | 183 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2010 |
Externally published | Yes |
Keywords
- AP214
- ischemia
- kidney
- nephrectomy
ASJC Scopus subject areas
- Urology