13. New recent data:
Intensive Care Over Nations
• ICON
• 10069 patients included
• 30% sepsis, 70% non-sepsis
• In sepsis patients: 67% AKI
• In non-sepsis patients: 57% AKI
14. Kinetics of AKI
0 20 40 60 80 100
Percentage (%)
No AKI
Risk
Injury
Failure
AKI in first 48h at ICU020406080100
Sepsis
Percentage(%)
Kinetics of AKI
Follow-up until day 7
22. AKI - AP depletion in damaged renal cortex
AP levels are depleted in
Acute Kidney Injury*
Ischemia (in min)
*Khundmiri et al. Am. J. Physiol. 273 (Renal Physiol. 42): F849–F856, 1997
23. Alkaline Phosphatase (AP)
• Dephosphorylating enzyme1
• Detoxifying properties
• Localized in kidney
• Improved renal function with AP treatment in patients with sepsis-associated AKI2,3
• Two phase-IIa clinical trials
1
Coleman et al. Biophys Biomol Struct (1992)
24. AP-treatment improves kidney function in patients with AKI, and prevents AKI occurrence
First Phase-II Study
Sepsis patients (n=36)Sepsis patients (n=36)
AKI at baseline (n=16)AKI at baseline (n=16) No AKI at baseline (n=20)No AKI at baseline (n=20)
Reduced RRT RequirementReduced RRT Requirement
Placebo biAP
0
20
40
60
80
100
%needforRRT
(4/5)
(4/11)
AKI occurrence after start of studyAKI occurrence after start of study
Placebo biAP
0
20
40
60
80
100
%AKI
(4/6)
(4/14)
Heemskerk et al. Crit Care Med (2009)
25. Second Phase-II Study in AKI with bovine AP
Bolus 67.5 U/kg, maintenance 132.5 U/kg/24 hrs during 48 hrs
26. recAP is a recombinant chimeric
human alkaline phosphatase
27. Human recAP AKI Development Plan
27
2012201220122012 2013201320132013 2014201420142014 2015201520152015
recAP DevelopmentrecAP Development
Animal testing
and tox study
Animal testing
and tox study
recAP ManufacturerecAP Manufacture
FDA &
EMA
FDA &
EMA
Phase IPhase I
Phase IIPhase II
Pre-clinical
PK/PD/dose
finding
Pre-clinical
PK/PD/dose
finding
28. Conclusions
• Diminished kidney function is frequent and influences outcome
• Different mechanisms of action are relevant,
during different windows of oppertunity to interfer
• Staging of AKI is difficult
• Determination of renal function is challenging
• Do the simple things right
• It’s a challenge
29. • Alkaline Phosphatase appears to limit AKI in sepsis patients
• A new phase 2 trial with human recAP is currently being conducted
Conclusions
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