Introduction: To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced\r\nacute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients\r\nwith severe sepsis or septic shock with evidence of AKI was performed.\r\nMethods: Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response\r\nSyndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis\r\nintervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of\r\nalkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h\r\nfor 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The\r\nprimary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement\r\nand duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes\r\nin circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.\r\nResults: There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary\r\noutcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28)\r\nwas significantly higher in the treated group relative to placebo (from 50 �± 27 to 108 �± 73 mL/minute (mean �±\r\nSEM) for the AP group; and from 40 �± 37 to 65 �± 30 mL/minute for placebo; P = 0.01). Reductions in RRT\r\nrequirement and duration did not reach significance. The results in renal parameters were supported by\r\nsignificantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding\r\nprotein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to\r\nplacebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.\r\nConclusions: The improvements in renal function suggest alkaline phosphatase is a promising new treatment for\r\npatients with severe sepsis or septic shock with AKI.
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