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

Critical Care

Johannes G van der Hoeven⁸  Wilbert HM Peters^1,10  Michael Bulitta¹  Herbert Spapen⁴  Philippe G Jorens⁷  Albertus Beishuizen⁹  Jean-Louis Vincent²  Pierre-François Laterre³  Jeroen Schouten⁵  Suzanne Heemskerk⁶  Peter Pickkers⁸ 

[1] CRM Biometrics GmbH, Weiherstrasse 19, Rheinbach, 53359, Germany;Department of Intensive Care Medicine, Hopital Erasme, Université Libre de Bruxelles, Route de Lennik 808, Brussels, 1070, Belgium;Department of Intensive Care Medicine, Cliniques Universitaires Saint Luc-UCL, Avenue Hippocate 10, Brussels, 1200, Belgium;Department of Intensive Care Medicine, University Hospital VUB, Laarbeeklaan 101, 1090, Jette, Belgium;Department of Critical Care Medicine, Canisius Wilhelmina Ziekenhuis, Weg door Jonkerbos 100, Nijmegen, 6532 SZ, The Netherlands;Department of Pharmacology and Toxicology, Institute for Genetic and Metabolic Disease, Geert Grooteplein Noord 21, Nijmegen, 6525 EZ, Radboud University Nijmegen Medical Center, The Netherlands;Department of Intensive Care Medicine, University Medical Center Antwerp, Wilrijkstraat 10, Edegem, 2650, Belgium;Department of Intensive Care, Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 10, Nijmegen, 6525 GA, The Netherlands;Department of Intensive Care Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, 1007 MB, The Netherlands;Department of Gastroenterology, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 8, Nijmegen, 6525 GA, The Netherlands

关键词: therapy;    acute renal failure;    septic shock;    systemic inflammatory response syndrome;    sepsis;   

Others  :  1093197
DOI  :  10.1186/cc11159

 received in 2011-09-27, accepted in 2012-01-23,  发布年份 2012

【 摘 要 】

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

【 授权许可】

   
2012 Pickkers et al.; licensee BioMed Central Ltd.

【 图 表 】

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