Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

Abstract

Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.