January 23, 2019

AKI Section Article Review - EJRC

Effect of alkaline phosphatase on short-term kidney function in critically ill patients with sepsis-associated AKI

 

Pickkers et al. performed an international randomised, double-blind, placebo-controlled, 4 parallel-group, dose-finding, adaptive phase 2a/2b trial to study the effects of human recombinant alkaline phosphatase on kidney function in critically ill patients with sepsis- associated AKI.

The trial consisted of 2 parts. Dose finding was conducted in part 1 and comprised the administration of recombinant alkaline phosphatase once daily for three days randomised to three different doses (0.4 mg/kg, 0.8 mg/kg, 1.6 mg/kg) or placebo (approximately n=30 per group). After 1.6 mg/kg was determined to be the optimal dose, it was compared with placebo in part 2 (n = 221). The primary end point was effect on kidney function as measured by the time-corrected area under the curve of the endogenous creatinine clearance (ECC) for days 1 through 7, divided by 7, providing a mean daily creatinine clearance. In total, 301 patients were enrolled.

 

STUDY STRENGTHS & LIMITATIONS

Treatment with recombinant alkaline phosphatase did not result in an improvement of kidney function in the first week after treatment (absolute difference in ECC 9.5 ml/min; p=0.47), but after 28 days, kidney function improved significantly compared with placebo (mean difference in ECC 18.5 ml/min; p=0.006). Interestingly, a significant effect of alkaline phosphatase on mortality was observed. All- cause mortality was lower in the 1.6 mg/kg alkaline phosphatase group at day 28 (14.4% vs 26.7%, p=0.02) and at day 90 (17.1% vs 29.3%, p=0.03) compared with placebo.

 

TAKE HOME MESSAGE
  • While human recombinant alkaline phosphatase did not improve short-term kidney function, there was a significant improvement in kidney function after 28 days.
  • Alkaline phosphatase may have a significant and positive effect on mortality in critically ill patients with sepsis-associated AKI.
  • A larger study looking at mortality as the primary outcome is warranted.

 

This article review was prepared and submitted by Sebastian J Klein, Department of Internal Medicine, Medizinische Universität Innsbruck, on behalf of the ESICM AKI Section and Journal Review Club.


REFERENCES

1) Pickkers P, Mehta RL, Murray PT, et al. Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury: A Randomized Clinical Trial. JAMA.2018;320(19):1998–2009. doi:10.1001/jama.2018.14283

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