Alkaline Phosphatase as a novel drug for Acute Kidney Injury during Septic Shock

Onclin, Marrit (2021) Alkaline Phosphatase as a novel drug for Acute Kidney Injury during Septic Shock. Master's Thesis / Essay, Medical Pharmaceutical Sciences.

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Abstract

The mortality of patients in the ICU due to Acute Kidney Injury (AKI) caused by septic shock accounts for more than 50%. Despite this, no real treatment is currently available except for kidney replacement therapy. AKI during sepsis or septic shock may be caused due to gram-negative bacteria which release LPS into the body, activating an anti-inflammatory response. Alkaline Phosphatase (AP) might be the first candidate that would directly lower the toxicity of LPS. Poelstra et al. (1997) were the first research group that researched the natural substrate of AP. They found that the sensitivity to LPS increased when AP was inhibited. Pickkers et al. (2012) researched what effect this would have on the human kidneys. Using Bovine intestinal AP on ICU patients with a gram-negative infection, it was found that the mortality rate decreased. Kiffer-Moreira et al. (2014) developed a human recombinant AP which was more stable while maintaining its specificity. Testing was repeated using this recAP and still showed positive results in the early clinical trials. The phase II clinical trial using recombinant AP did not show significant improvement after seven days. However, after a post hoc analysis, a significant improvement was detected in both treatment effect and all-cause mortality after a 28-day period. A phase III clinical trial is currently running with a COVID-19 cohort recently announced. Looking at the results of earlier studies and the high incidence of AKI among COVID-19 pat

Item Type:	Thesis (Master's Thesis / Essay)
Supervisor name:	Poelstra, K.
Degree programme:	Medical Pharmaceutical Sciences
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	01 Dec 2021 12:30
Last Modified:	01 Dec 2021 12:30
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/26320

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