Introduction

Sepsis-associated acute kidney injury (AKI) has adverse effects on long-term kidney outcomes and survival. In such cases, use of detoxifying enzyme alkaline phosphatase may improve kidney function and survival.

Research question

Does the human recombinant alkaline phosphatase improve kidney function in patients who are critically ill with sepsis-associated acute kidney injury?

Methodology

An international trial (53 sites), randomized, double-blind placebo-controlled, dose-finding, adaptive phase 2a/2b study involving 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI.

The primary outcome was the time-corrected area under the curve of the endogenous creatinine clearance (ECC) for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance. Incidence of fatal and serious adverse events was also measured. The follow-up was conducted for 90 days.

The intervention included administering recombinant alkaline phosphatase in a dosage of 0.4 mg/Kg (n=31), 0.8 mg/Kg (n=32), or 1.6 mg/Kg (n=29), or placebo (n=30), once daily for 3 days in randomized patients. The optimal dose was identified as 1.6 mg/Kg depending on modeling approaches and adverse reactions.

In another part of the trial, 1.6 mg/Kg (n=82) was compared with placebo (n=86).

Results

It was seen that median ECC increased from 26.0mL/min to 65.4 mL/min in the recombinant alkaline phosphatase 1.6 mg/Kg group vs from 35.9 mL/min to 61.9 mL/min in the placebo group; from day 1 to day 7.

Conclusion

The study results showed that among patients who were critically ill with sepsis-related acute kidney injury, human recombinant alkaline phosphatase compared with placebo did not significantly short-term kidney function. Adverse reactions were reported in most patients, independent of treatment with recombinant alkaline phosphatase or placebo. There were no reports of any compound-specific or dose-related adverse effects from the trial.

Reference

1. Pickkers P, Mehta RL, Murray PT, Joannidis M, et al. Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in aptients with sepsis-associated acute kidney injury A Randomized clinical trial. JAMA. 2018; 320: 1998-2009.