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Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: A prospective randomized double-blind placebo-controlled trial

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Pickkers, Peter [Radboud University Nijmegen Medical Center] Heemskerk, Suzanne [Radboud University Nijmegen Medical Center] Schouten, Jeroen [Department of Critical Care Medicine, Canisius Wilhelmina Ziekenhuis] Laterre, Pierre-François [UCL] Vincent, Jean-Louis [Hopital Erasme, Université Libre de Bruxelles] van der Hoeven, Johannes G. [Radboud University Nijmegen Medical Center]

Introduction: To evaluate whether alkaline phosphatase (AP) treatment improves renal function in sepsis-induced acute kidney injury (AKI), a prospective, double-blind, randomized, placebo-controlled study in critically ill patients with severe sepsis or septic shock with evidence of AKI was performed.Methods: Thirty-six adult patients with severe sepsis or septic shock according to Systemic Inflammatory Response Syndrome criteria and renal injury defined according to the AKI Network criteria were included. Dialysis intervention was standardized according to Acute Dialysis Quality Initiative consensus. Intravenous infusion of alkaline phosphatase (bolus injection of 67.5 U/kg body weight followed by continuous infusion of 132.5 U/kg/24 h for 48 hours, or placebo) starting within 48 hours of AKI onset and followed up to 28 days post-treatment. The primary outcome variable was progress in renal function variables (endogenous creatinine clearance, requirement and duration of renal replacement therapy, RRT) after 28 days. The secondary outcome variables included changes in circulating inflammatory mediators, urinary excretion of biomarkers of tubular injury, and safety.Results: There was a significant (P = 0.02) difference in favor of AP treatment relative to controls for the primary outcome variable. Individual renal parameters showed that endogenous creatinine clearance (baseline to Day 28) was significantly higher in the treated group relative to placebo (from 50 ± 27 to 108 ± 73 mL/minute (mean ± SEM) for the AP group; and from 40 ± 37 to 65 ± 30 mL/minute for placebo; P = 0.01). Reductions in RRT requirement and duration did not reach significance. The results in renal parameters were supported by significantly more pronounced reductions in the systemic markers C-reactive protein, Interleukin-6, LPS-binding protein and in the urinary excretion of Kidney Injury Molecule-1 and Interleukin-18 in AP-treated patients relative to placebo. The Drug Safety Monitoring Board did not raise any issues throughout the trial.Conclusions: The improvements in renal function suggest alkaline phosphatase is a promising new treatment for patients with severe sepsis or septic shock with AKI.Trial Registration: www.clinicaltrials.gov: NCTNCT00511186. © 2012 Pickkers et al.; licensee BioMed Central Ltd.

Document type Article de périodique (Journal article)
Access type Accès libre
Publication date 2012
Language Anglais
Journal information "AACN Advanced Critical Care" - Vol. 16, no. 1, p. R14 (2012)
Peer reviewed yes
Publisher Springer
issn 1559-7768
e-issn 1559-7776
Publication status Publié
Affiliations UCL - SSS/IREC/MEDA - Pôle de médecine aiguë
UCL - (SLuc) Service de soins intensifs
Keywords Acute renal failure ; Sepsis ; Septic shock ; Systemic inflammatory response syndrome ; Therapy
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Bibliographic reference Pickkers, Peter ; Heemskerk, Suzanne ; Schouten, Jeroen ; Laterre, Pierre-François ; Vincent, Jean-Louis ; et. al. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: A prospective randomized double-blind placebo-controlled trial. In: AACN Advanced Critical Care, Vol. 16, no. 1, p. R14 (2012)
Permanent URL http://hdl.handle.net/2078.1/122705